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Relations du système plasminogène-plasmine et cancer

Étude moléculaire de facteurs liés à l’invasivité et à la néoangiogenèse. PAI1, PAI2, uPA, uPAR valeur pronostique et cibles thérapeutiques potentielles

The plasmin/plasminogen system and cancer

Molecular study of factors associated with invasiveness and tumour angiogenesis. PAI1, PAI2, uPA, uPAR: prognostic value and potential therapeutic targets

  • Biologie Du Cancer / Cancer Biology
  • Published:
Oncologie

Abstract

Proteases play a central role in tissue repair and in the process of tumour growth and invasiveness. However, almost all of the proteolytic enzymes are secreted as inactive pro-proteases. With the exception of cathepsin D, which is capable of auto-activation, all the other proteases are activated by a common mechanism involving plasmin, which is itself derived from conversion of plasminogen, an ubiquitous pro-molecule.

uPA initiates the conversion of plasminogen to the activated form, plasmin. The specific uPAR receptor is located on the external surface of the cell membrane. It does not have a trans-membrane component and is not linked to pathways of intracellular signal transduction. uPAR, however, can form heterodimers with other membrane molecules, such as growth factor receptors, cellular adhesion molecules etc. When these trans-membrane molecules form heterodimers with uPAR, they activate the pathways of signal transduction, with which they are associated. uPAR is essential for the activation of uPA, but also for cellular motility associated with integrin αvβ3. The uPAR - αvβ3 complex is formed on the leading edge of the lamellipodia of migrating cells (EMT positive cancerous epithelial cells and activated endothelial cells).

PAI1 actively inhibits uPA activity and has a complex role in tumorigenesis:

  1. 1.

    in cell migration during invasion or angiogenesis, it detaches the uPAR - αvβ3 complex which is bound to vitronectin and other ligands through uPA. This detachment at the posterior pole of motile cells results from the greater affinity of PAI1 at the uPA binding site on vitronectin. This allows uPAR to be internalised and its re-appearance at the leading edge of the cell.

  2. 2.

    a second and very significant effect is its leading role in transient stabilisation of new capillaries through cooperation between endothelial cells and pericytes, which ensures that the new vessels are functional.

    This scientific evidence has been assessed by a European expert group with laboratory and clinical input and, in compliance with Hayes’ criteria, has led to the establishment of uPA and PAI1as prognostic factors at the highest level of evidence (LOE-I) in breast cancer without node involvement. Together with hormone receptors ER PR and the membrane receptor HER2, these are the only parameters of LOE-I category for breast cancer, and they have appeared as such in international recommendations since 2007 and in the national recommendations of 2009.

Résumé

Les protéases jouent un rôle crucial dans la réparation tissulaire et le processus de croissance et invasivité tumorale. Cependant sur le plan physiopathologique, la quasi totalité de ces enzymes protéolytiques sont sécrétées sous forme de proprotéases inactives. A l’exception de la cathepsine D qui est capable de s’autoactiver, l’ensemble des autres protéases sont activées par un mécanisme commun à partir de la plasmine, elle-même dérivant de la transformation du plasminogène, pro molécule ubiquitaire.

uPA est l’initiateur de la transformation activatrice du plasminogène en plasmine. Son récepteur spécifique uPAR est un récepteur de surface extra membranaire, sans domaine transmembranaire ni relié à des voies de transduction du signal intracellulaires. uPAR est cependant capable de s’hétérodimériser avec d’autres molécules membranaires (récepteurs des facteurs de croissance, molécules d’adhésion cellulaire....).

Ces molécules transmembranaires, après hétérodimérisation avec uPAR, activent les voies de transduction du signal qui leur sont associées. uPAR est indispensable pour l’activation de uPA, mais également pour la mobilisation cellulaire en association avec le complexe intégrines αvβ3. L’hétérodimérisation uPAR - αvβ3 se fait au front antérieur des lamellipodes des cellules mobilisables (cellules épithéliales cancéreuses EMT positives, cellules endothéliales activées, macrophages associés aux tumeurs, néofibroblastes...).

PAI1, inhibiteur actif de l’activité uPA, a un rôle complexe dans la tumorigenèse:

  1. 1.

    dans la mobilisation cellulaire, au cours de l’invasion ou de l’angiogenèse, il détache l’hétérodimère uPAR - αvβ3 relié au substrat vitronectine, entre autres via uPA. Ce détachement au pôle postérieur des cellules mobiles est possible par la plus grande affinité de PAI1 au site de liaison à la vitronectine de uPA. Ce détachement permet l’internalisation de uPAR et sa réexposition au pôle antérieur cellulaire.

  2. 2.

    un second rôle très important est son rôle capital dans la stabilisation transitoire des néocapillaires, la coopération entre cellules endothéliales et cellules péricytaires, cela permettant une néoangiogenèse fonctionnelle.

    L’ensemble de ces données fondamentales, associé à une expertise biologique et clinique dans un réseau européen, selon les critères définis par Hayes [277a] ont permis de faire de uPA PAI1 des facteurs pronostiques de niveau d’évidence maximum (LOE I) pour les cancers du sein sans envahissement ganglionnaire. Ce sont les seuls paramètres de LOE I dans le cancer du sein s’ajoutant aux récepteurs hormonaux RE RP et au récepteur membranaire HER2. Cela apparaît dans les recommandations internationales dès 2007 et dans les recommandations nationales en 2009.

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Références

  1. Al-Ejeh F, Croucher D, Ranson M (2004) Kinetic analysis of plasminogen activator inhibitor type-2: urokinase complex formation and subsequent internalisation by carcinoma cell lines. Exp Cell Res 297: 259–71

    PubMed  CAS  Google Scholar 

  2. Alessi MC, Chomiki N, Berthier R, et al. (1994) Detection of plasminogen activator inhibitor 1 (PAI1) mRNA in human megakaryocytes by in situ hybridization. Thrombo Haemost 72: 931–6

    CAS  Google Scholar 

  3. Allen BJ, Rizvi S, Li Y, et al. (2001) In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers. Crit Rev Oncol Hematol 39: 139–46

    PubMed  CAS  Google Scholar 

  4. Allen BJ, Tian Z, Rizvi SM, et al. (2003) Preclinical studies of targeted therapy for breast cancer using 213 bi-labelled-plasminogen activator inhibitor type-2. Br J Cancer 88: 944–50

    PubMed  CAS  Google Scholar 

  5. Andreasen PA, Georg B, Lund LR, et al. (1990) Plasminogen activator inhibitors: hormonally regulated serpins. Mol Cell Endocrinol 68: 1–19

    PubMed  CAS  Google Scholar 

  6. Andreasen PA, Kjoller L, Christensen L, Duffy MJ (1997) The urokinase-type plasminogen activator system in cancer metastasis (review). Int J Cancer 72: 1–22

    PubMed  CAS  Google Scholar 

  7. Andreasen PA, Nielsen LS, Kristensen P, et al. (1986) Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinase-type plasminogen activator, but no its proenzyme. J Biol Chem 261: 7644–51

    PubMed  CAS  Google Scholar 

  8. Andreasen PA, Riccio A, Walinder KG, et al. (1986) Plasminogen activator inhibior type 1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing. FEBS Lett 206: 213–8

    Google Scholar 

  9. Andreasen PA, Sottrup Jensen L, Kjoller L, et al. (1994) Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes. FEBS Lett 338: 239–45

    PubMed  CAS  Google Scholar 

  10. Axelrod JH, Reich R, Miskin R (1989) Expression of human recombinant plasminogen activators enhances invasion and experimental metastasis of H-ras-transformed NIH 3T3 cells. Mol Cell Biol 9: 2133–41

    PubMed  CAS  Google Scholar 

  11. Bacharach E, Itin A, Keshet E (1992) In vivo patterns of expression of urokinase and its inhibitor PAI1 suggest a concerted role in regulating physiological angiogenesis. Proc Natl Acad Sci USA 89: 10686–90

    PubMed  CAS  Google Scholar 

  12. Bachmann F (1995) The enigma PAI2. Gene expression, evolutionary and functional aspects. Thromb Haemost 74: 172–9

    PubMed  CAS  Google Scholar 

  13. Bajou K, Noel A, Gerard RD, et al. (1998) Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 4: 923–8

    PubMed  CAS  Google Scholar 

  14. Bajou K, Peng H, Laug WE, et al. (2008) Plasminogen activator inhibitor 1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell 14: 324–34

    PubMed  CAS  Google Scholar 

  15. Baramova EN, Bajou K, Remacle A, et al. (1997) Involvement of pa/plasmin system in the processing of pro-mmp-9 and the second step of pro-mmp-2 activation. FEBS Letters 405: 157–62

    PubMed  CAS  Google Scholar 

  16. Behrendt N, List K, Andreasen PA, Dano K (2003) The pro-urokinase plasminogen-activation system in the presence of serpin-type inhibitors and the urokinase receptor: rescue of activity through reciprocal pro-enzyme activation. Biochem J 371: 277–87

    PubMed  CAS  Google Scholar 

  17. Behrendt N, Ploug M, Patthy L, et al. (1991) The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator. J Biol Chem 266: 7842–7

    PubMed  CAS  Google Scholar 

  18. Behrendt N, Ronne E, Dano K (1996) Domain interplay in the urokinase receptor-requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains. J Biol Chemistry 271: 22885–94

    CAS  Google Scholar 

  19. Behrendt N, Stephens RW (1998) The urokinase receptor. Fibrinolysis & Proteolysis 12: 191–205

    CAS  Google Scholar 

  20. Bianchi E, Cohen RL, Dai A, et al. (1995) Immunohistochemical localization of the plasminogen activator inhibitor 1 in breast cancer. Int J Cancer 60: 597–603

    PubMed  CAS  Google Scholar 

  21. Bini A, Itoh Y, Kudryk BJ, Nagasse H (1996) Degradation of cross-linked fibrin by matrix metalloproteinase-3 (stromelysin-1): hydrolysis of the gamma Gly 404-Ala 405 peptide bond. Biochemistry 35: 13056–63

    PubMed  CAS  Google Scholar 

  22. Blaisi F, Vassalli JD, Dano K (1987) Urokinase-type plasminogen activator: proenzyme, receptor and inhibitors. J Cell Biol 104: 801–4

    Google Scholar 

  23. Bode W, Huber R (1992) Natural protein proteinase inhibitors and their interaction with proteinases. Eur J Biochem 204: 433–51

    PubMed  CAS  Google Scholar 

  24. Borstnar S, Vrhovec I, Cufer T (2002) Prognostic value of plasminogen activator inhibitors in breast cancer. Int J Biol Markers 17: 96–103

    PubMed  CAS  Google Scholar 

  25. Borstnar S, Vrhovec I, Svetic B, Cufer T (2002) Prognostic value of the urokinase-type plasminogen activator, and its inhibitors and receptor in breast cancer patients. Clin. Breast Cancer 3: 138–46

    PubMed  CAS  Google Scholar 

  26. Bouchet C, Ferrero-Pous M, Hacene K, et al. (2003) Limited prognostic value of c-erbB-2 compared to uPA and PAI1 in primary breast carcinoma. Int J Biol Markers 18(3): 207–17

    PubMed  CAS  Google Scholar 

  27. Bouchet C, Hacene K, Martin PM, et al. (1999) Dissemination risk index based on plasminogen activator system components in primary breast cancer. J Clin Oncol 17(10): 3048–57

    PubMed  CAS  Google Scholar 

  28. Bouchet C, Hacene K, Martin PM, et al. (2000) Breast cancer: prognostic value of a dissemination index based on 4 components of the urokinase-type plasminogen activator system. Pathol Biol (Paris) 48(9): 825–31

    CAS  Google Scholar 

  29. Bouchet C, Spyratos F, Martin PM, et al. (1994) Prognostic value of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI1 and PAI2 in breast carcinomas. Br J Cancer 69(2): 398–405

    PubMed  CAS  Google Scholar 

  30. Bouchet C, Spyratos F, Martin PM, et al. (1994) Prognostic value of urokinase-type plasminogen activator and 2 inhibitors PAI1 and PAI2 in breast cancer. Bull Cancer 81(9): 770–9

    PubMed  CAS  Google Scholar 

  31. Bouchet C, Spyratos F, Martin PM, et al. (1994) Prognostic value of urokinase- type plasminogen activator (uPA) and plasminogen activator inhibitors PAI1 and PAI2 in breast carcinomas. Br J Cancer 69: 398–405

    PubMed  CAS  Google Scholar 

  32. Bouchet-Bernet C, Spyratos F, Andrieu C, et al. (1996) Influence of the extraction procedure on plasminogen activator inhibitor-2 (PAI2) and urokinase receptor (uPAR) assays in breast cancer tissues. Breast Cancer Res Treat 41(2): 141–6

    PubMed  CAS  Google Scholar 

  33. Braaten JV, Handt S, Jerome WG, et al. (1993) Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor-1: light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus. Blood 81: 1290–9

    PubMed  CAS  Google Scholar 

  34. Broet P, Spyratos F, Romain S, et al. (1999) Prognostic value of uPA and p53 accumulation measured by quantitative biochemical assays in 1245 primary breast cancer patients: a multicentre study. Br J Cancer 80(3–4): 536–45

    PubMed  CAS  Google Scholar 

  35. Brückner A, Filderman AE, Kirchheimer JC, et al. (1992) Endogenous receptor-bound urokinase mediates tissue invasion of the human lung carcinoma cell lines A549 and Calu-1. Cancer Res 52: 3043–7

    PubMed  Google Scholar 

  36. Buo L, Lyberg T, Jorgensen L, et al. (1993) Location of plasminogen activator (PA) and PA inhibitor in human colorectal adenocarcinomas. APMIS 101: 235–41

    PubMed  CAS  Google Scholar 

  37. Caccarno DV, Keohane ME, McKeever PE (1994) Plasmiogen activators and inhibitors in gliomas: an immunohistochemical study. Mod Pathol 7: 99–104

    Google Scholar 

  38. Cajot JF, Barnat J, Bergonzelli GE, et al. (1990) Plasminogen-activator inhibitor type-1 is a potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinomal cells. Proc Natl Acad Sci USA 87: 6939–43

    PubMed  CAS  Google Scholar 

  39. Carrell RW, Stein PE (1996) The biostructural pathology of the serpins-critical function of sheet opening mechanism (review). Biol Chem Hoppe-Seyler 377: 1–17

    PubMed  CAS  Google Scholar 

  40. Chappuis PO, Dieterich B, Sciretta V, et al. (2001) Functional evaluation of plasmin formation in primary breast cancer. J Clin Oncol 19: 2731–8

    PubMed  CAS  Google Scholar 

  41. Christensen L, Simonsen ACW, Heegaard CW, et al. (1996) Immunohistochemical localization of urokinase-type plasminogen activator, type-1 plasminogen-activator inhibitor, urokinase receptor and alpha(2)-macroglobulin receptor in human breast carcinomas. Int J Cancer 66: 441–52

    PubMed  CAS  Google Scholar 

  42. Collen D (1980) On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemost 43: 77–89

    PubMed  CAS  Google Scholar 

  43. Croucher D, Saunders DN, Ranson M (2006) The urokinase/ PAI2 complex: a new high affinity ligand for the endocytosis receptor low density lipoprotein receptor-related protein. J Biol Chem 281: 10206–13

    PubMed  CAS  Google Scholar 

  44. Croucher DR, Saunders DN, Lobov S, Ranson M (2008) Revisiting the biological roles of PAI2 (Serpin B2) in cancer. Nat Rev Cancer 8(7): 535–45

    PubMed  CAS  Google Scholar 

  45. Croucher DR, Saunders DN, Stillfried GE, Ranson M (2007) A structural basis for differential cell signalling by PAI1 and PAI2 in breast cancer cells. Biochem J 408: 203–10

    PubMed  CAS  Google Scholar 

  46. Cubellis MV, Nolli ML, Cassani G, Blasi F (1986) Binding of single-chain prourokinase to the urokinase receptor of human U937 cells. J Biol Chem 261: 15819–22

    PubMed  CAS  Google Scholar 

  47. Czekay RP, Aertgeerts K, Curriden SA, Loskutoff DJ (2003) Plasminogen activator inhibitor 1 detaches cells from extracellular matrices by inactivating integrins. J Cell Biol 160: 781–91

    PubMed  CAS  Google Scholar 

  48. Dano K, Andreasen PA, Grondahl Hansen J, et al. (1985) Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 44: 139–266

    PubMed  CAS  Google Scholar 

  49. Dano K, Behrendt N, Brünner N, et al. (1994) The urokinase receptor. Protein structure and role in plasminogen activation and cancer invasion. Fibrinolysis 8(suppl. 1): 189–203

    Google Scholar 

  50. Dano K, Moller V, Ossowski L, Nielsen LS (1980) Purification and characterization of a plasminogen activator from mouse cells transformed by an oncogenic virus. Biochim Biophys. Acta 613: 542–55

    PubMed  CAS  Google Scholar 

  51. Dawson S, Henney A (1992) The status of PAI1 as a risk factor for arterial and thrombotic disease(a review). Atherosclerosis 95: 105–17

    PubMed  CAS  Google Scholar 

  52. De Fouw NJ, van Hinsbergh VW, De Jong YF, et al. (1987) The interaction of activated protein C and thrombin with the plasminogen activator inhibitor released from human endothelial cells. Thromb Haemost 57: 176–82

    PubMed  Google Scholar 

  53. De Vries TJ, Quax PH, Denijn M, et al. (1994) Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression. Am J Pathol 144: 70–81

    PubMed  Google Scholar 

  54. Dear AD, Medcalf RL (1995) The cellular and molecular biology of plasminogen activator inhibitor type-2 (review). Fibrinolysis 9: 321–30

    CAS  Google Scholar 

  55. Declerck PJ, De Mol M, Alessi MC, et al. (1988) Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). J Biol Chem 263: 15454–61

    PubMed  CAS  Google Scholar 

  56. Declerck PJ, De Mol M, Vaughan DE, Collen D (1992) Identification of a conformationally distinct form of plasminogen activator inhibitor-1, acting as a nonhibitory substrate for tissue-type plasminogen activator. J Biol Chem 267: 11693–6

    PubMed  CAS  Google Scholar 

  57. Degryse B, Neels JG, Czekay RP, et al. (2004) The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1. J Biol Chem 279: 22595–604

    PubMed  CAS  Google Scholar 

  58. Delbado C, Masouye I, Saurat JH, et al. (1994) Plasminogen activation in melanocytic neoplasia. Cancer Res 54: 1547–52

    Google Scholar 

  59. Delbaldo C, Cunningham M, Vassalli JD, Sappino AP (1995) Plasmin-catalyzed proteolysis in colorectal neoplasia. Cancer Res 55: 4688–95

    PubMed  CAS  Google Scholar 

  60. Deng G, Curriden SA, Wang SJ, et al. (1996) Is plasminogen activator inhibitor 1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J Cell Biol 134: 1563–71

    PubMed  CAS  Google Scholar 

  61. Deng G, Royle G, Seiffert D, Loskutoff DJ (1995) The PAI1 vitronectin interaction: two cats in a bag. Thromb Haemost 74: 66–70

    PubMed  CAS  Google Scholar 

  62. Duffy MJ, Duggan C (2004) The urokinase plasminogen activator system: a rich source of tumour marker for the individualised management of patients with cancer. Clin Biochem 37: 541–8

    PubMed  CAS  Google Scholar 

  63. Duffy MJ, Reilly D, O’sullivan C, et al. (1990) Urokinase-plasminogen activator, a new and independant prognosistic marker in breast cancer. Cancer Res 50: 6827–9

    PubMed  CAS  Google Scholar 

  64. Duggan C., Kennedy S, Kramer MD, et al. (1997) Plasminogen activator inhibitor type-2 in breast cancer. Br J Cancer 76: 622–7

    PubMed  CAS  Google Scholar 

  65. Ehrlich HJ, Gebbink RK, Keijer J, et al. (1990) Alteration of serpin specificity by a protein cofactor. Vitronectin endows plasminogen activator inhibitor-1with thrombin inhibitory properties. J Biol Chem 265: 13029–35

    PubMed  CAS  Google Scholar 

  66. Ehrlich HJ, Gebbink RK, Keijer J, Pannekoek H (1992) Elucidation of structural requirements on plasminogen activator inhibitor 1 for binding to heparin. J Biol Chem 267: 11606–11

    PubMed  CAS  Google Scholar 

  67. Ehrlich HJ, Gebbink RK, Preissner KT, et al. (1991) Thrombin neutralizes plasminogen activator inhibitor 1 (PAI1) that is complexed with vitronectin in the endothelial cell matrix. J Cell Biol 115: 1773–81

    PubMed  CAS  Google Scholar 

  68. Ehrlich HJ, Keijer J, Preissner KT, et al. (1991) Functional interaction of plasminogen activaor inhibitor type-1 (PAI1) and hepatin. Biochemistry 30: 1021–8

    PubMed  CAS  Google Scholar 

  69. Ellis V, Behrendt N, Dano K (1991) Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor. J Biol Chem 266: 12752–

    PubMed  CAS  Google Scholar 

  70. Ellis V, Pyke C, Eriksen J, et al. (1992) The urokinase receptor: involvement in cell surface proteolysis and cancer invasion. Ann N Y Acad Sci 667: 13–31

    PubMed  CAS  Google Scholar 

  71. Ellis V, Wun TC, Behrendt N, et al. (1990) Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors. J Biol Chem 265: 9904–8

    PubMed  CAS  Google Scholar 

  72. Estreicher A, Muhlhauser J, Carpentier JL, et al. (1990) The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. J Cell Biol 111: 783–92

    PubMed  CAS  Google Scholar 

  73. Fa M, Karolin J, Aleshkov S, et al. (1995) Time-resolved polarized fluorescence spectroscopy studies of plasminogen antivator inhibior type 1: conformational changes of the reactive center upon interactions with target proteases, vitronectin and heparin. Biochemistry 34: 13833–40

    PubMed  CAS  Google Scholar 

  74. Foekens JA, Buessecker F, Peters HA, et al. (1995) Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer. Cancer Res 55: 1423–7

    PubMed  CAS  Google Scholar 

  75. Foekens JA, Schmitt M, van Putten WL, et al. (1994) Plasminogen activator inhibitor 1 and prognosis in primary breast cancer. J Clin Oncol 12: 1648–58

    PubMed  CAS  Google Scholar 

  76. Fong KM, Kida Y, Zimmerman PV, Smith PJ (1996) TIMP1 and adverse prognosis in non-small cell lung cancer. Clin Cancer Res 2: 1369–72

    PubMed  CAS  Google Scholar 

  77. Foucre D, Bouchet C, Hacene K, et al. (1991) Relationship between cathepsin D, urokinase and plasminogen activator inhibitors in malignant vs benign breast tumours. Br J Cancer 64: 926–32

    PubMed  CAS  Google Scholar 

  78. Frandsen TL, Stephens RW, Pedersen AN, et al. (1998) Plasminogen activator inhibitor type-1 (PAI1) in cancer: a potential new target for anti nvasive and antimetastatic therapy. Drugs of the future 23: 873–83

    CAS  Google Scholar 

  79. Ganesh S, Sier CF, Griffioen G, et al. (1994) Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer. Cancer Res 54: 4065–71

    PubMed  CAS  Google Scholar 

  80. Gibson A, Baburaj K, Day DE, et al. (1997) The use of fluorescent probes to characterize conformational changes in the interaction between vitronectin and plasminogen activator inhibitor-1. J Biol Chem 272: 5112–21

    PubMed  CAS  Google Scholar 

  81. Gilabert J, Estrelles A, Grancha S, et al. (1995) Fibrinolytic system and reproductive process with special reference to fibrinolytic failure in pre-eclampsia. Human reproduction 9: 321–30

    Google Scholar 

  82. Ginsburg D, Zeheb R, Tang AY, et al. (1986) cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest 78: 1673–80

    PubMed  CAS  Google Scholar 

  83. Golder JP, Stephens RW (1983) Minactivin: a human monocyte product which specifically inactives urokinase-type plasminogen activators. Eur J Biochem 136: 517–22

    PubMed  CAS  Google Scholar 

  84. Goretski L, Schmitt M, Mann K, et al. (1992) Effective activation of the proenzyme form of the urokinase-type plasminogen activator (pro-uPA) by the cysteine protease cathepsin L. FEBS Lett 297: 112–8

    Google Scholar 

  85. Grignon DJ, Sakr W, Toth M, et al. (1996) High levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. Cancer Res 56: 1654–9

    PubMed  CAS  Google Scholar 

  86. Grondahl Hansen J, Kristensen P, Rosenquist C, et al. (1993) High levels of urokinase-type plasminogen activtor and its inhibitor PAI1 in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Res 53: 2513–21

    PubMed  CAS  Google Scholar 

  87. Grondahl-Hansen J, Ralkiaer E, Kirkeby LT, et al. (1991) Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans. Am J Pathol 138: 111–7

    PubMed  CAS  Google Scholar 

  88. Hagood JS, Olman MA, Godoy JA, et al. (1996) Regulation of type-1plasminogen activator inhibitor by fibrin degradation products in rat lung fibroblasts. Blood 87: 3749–57

    PubMed  CAS  Google Scholar 

  89. Harbeck N, Alt U, Berger U, Kates R, et al. (2000) Long-term follow-up confirms prognostic impact of PAI1 and cathepsin D and L in primary breast cancer. Int J Biol Markers 15(1): 79–83

    PubMed  CAS  Google Scholar 

  90. Harbeck N, Dettmar P, Thomssen C, et al. (1999) Risk-group discrimination in node-negative breast cancer using invasion and proliferation markers: 6-year median follow-up. Br J Cancer 80(3–4): 419–26

    Google Scholar 

  91. Harbeck N, Kates RE, Gauger K, et al. (2004) Urokinase-type plasminogen activator (uPA) and its inhibitor PAI1: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer. Thromb Haemost 91(3): 450–6

    PubMed  CAS  Google Scholar 

  92. Harbeck N, Kates RE, Look MP, et al. (2002) Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (N = 3,424). Cancer Res 62(16): 4617–22

    PubMed  CAS  Google Scholar 

  93. Harbeck N, Kates RE, Schmitt M (2002) Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type-1for individualized therapy decisions in primary breast cancer is greatest when used in combination. J Clin Oncol 20(4): 1000–7

    PubMed  Google Scholar 

  94. Harbeck N, Kates RE, Schmitt M, et al. (2004) Urokinase-type plasminogen activator and its inhibitor type-1predict disease outcome and therapy response in primary breast cancer. Clin Breast Cancer 5(5): 348–52

    PubMed  CAS  Google Scholar 

  95. Harbeck N, Schmitt M, Kates RE, et al. (2002) Clinical utility of urokinase-type plasminogen activator and plasminogen activator inhibitor 1 determination in primary breast cancer tissue for individualized therapy concepts. Clin Breast Cancer 3(3): 196–200

    PubMed  CAS  Google Scholar 

  96. Harris L, Fritsche H, Mennel R, et al. (2007) American society of clinical oncology (2007). Update of recommandations for the use of tumor markers in breast cancer. J Clin Oncol 25(33): 5287–312

    PubMed  CAS  Google Scholar 

  97. Haverkate F, Thompson SG, Duckert F (1995) Haemostasis factors in angina pectoris: results of the ECAT angina pectoris study group. Thromb Haemost 73: 561–7

    PubMed  CAS  Google Scholar 

  98. HE CS, Wilhelm SM, Pentland AP, et al. (1989) Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci USA 86: 2632–6

    PubMed  CAS  Google Scholar 

  99. Hekman CM, Loskutoff DJ (1988) Bovine plasminogen activator inhibitor-1: specificity determinations and comparison of the active, latend and guanidine-activated forms. Biochemistry 27: 2911–18

    PubMed  CAS  Google Scholar 

  100. Hekman CM, Loskutoss DJ (1985) Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 260: 11581–7

    PubMed  CAS  Google Scholar 

  101. Herz J, Strickland DK (2001) LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 108: 779–84

    PubMed  CAS  Google Scholar 

  102. Hill SA, Shaughnessy SG, Joshua P, et al. (1996) Differential mechanism targeting type-1plasminogen activator inhibitor and vitronectin into the storage granules of a human magakaryocytic cell line. Blood 87: 5061–73

    PubMed  CAS  Google Scholar 

  103. Hofmann R, Lehmer A, Buresch M, et al. (1996) Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer 78: 487–92

    PubMed  CAS  Google Scholar 

  104. Hofmann R, Lehmer A, Hartung R, et al. (1996) Prognostic value of urokinase plasminogen activator and plasminogen activator inhibitor 1 in renal cancer. J Urol 155: 858–62

    PubMed  CAS  Google Scholar 

  105. Hollas W, Blasi F, Boyd D (1991) Role of the urokinase receptor in facilitating extracellular matrix invasion by cultured colon cancer. Cancer Res 51: 3690–5

    PubMed  CAS  Google Scholar 

  106. Holst-Hansen C, Johannessen B, Hoyer-Hansen G, et al. (1996) Urokinase-type plasminogen activation in three human breast cancer cell lines correlates with their in vitro invasiveness. Clin Exp Metastasis 14: 297–307

    PubMed  CAS  Google Scholar 

  107. Holten-Andersen MN, Murphy G, Nielsen HJ, et al. (1999) Quantification of TIMP-2 in plasma of healthy blood donors and patients with advanced cancer. Br J Cancer 80: 495–503

    PubMed  CAS  Google Scholar 

  108. Hoyer Hansen G, Ploug M, Behrendt N, et al. (1997) Cell-surface acceleration of urokinase-catalyse receptor cleavage. Eur J Biochem. 243: 21–6

    Google Scholar 

  109. Hoyer Hansen G, Ronne E, Solberg H, et al. (1992) Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligand-binding domain. J biol Chem 267: 18224–9

    Google Scholar 

  110. Ishikawa N, Endo Y, Sasaki T (1996) Inverse correlation between mRNA expression of plasminogen activator inhibitor-2 and lymph node metastasis in human breast cancer. Jpn J Cancer Res 87: 480–7

    PubMed  CAS  Google Scholar 

  111. Jänicke F, Prechtl A, Thomssen C, et al. (2001) Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J Natl Cancer Inst 93(12): 913–20

    PubMed  Google Scholar 

  112. Jänicke F, Schmitt M, Graeff H (1991) Clinical relevance of the urokinase-type and tissue-type plasminogen activators and of their type-1inhibitor in breast cancer. Semin Thromb Hemost 17: 303–12

    PubMed  Google Scholar 

  113. Jänicke F, Schmitt M, Pache L, et al. (1993) Urokinase (uPA) and its inhibitor PAI1 are strong and independent prognostic factors in node-negative breast cancer. Breast Cancer Res Treat 24: 195–208

    PubMed  Google Scholar 

  114. Jankun J, Merrick HW, Goldblatt PJ (1993) Expression and localization of elements of the plasminogen activation system in benign breast disease and breast cancers. J Cell Biochem 53: 135–44

    PubMed  CAS  Google Scholar 

  115. Juhan-Vague I, Alessi MC, Joly P, et al. (1989) Plasma plasminogen activator inhibitor 1 in angina pectoris. Influence of plasma insulin and acute-phase response. Arteriosclerosis 9: 362–7

    PubMed  CAS  Google Scholar 

  116. Kaku T, Kamura T, Kinukawa N, et al. (1997) Angiogenesis in endometrial carcinoma. Cancer 80: 741–7

    PubMed  CAS  Google Scholar 

  117. Kanse SM, Kost C, Wilhelm OG, et al. (1996) The urokinase receptor is a major bitronectin-binding protein on endothelial cells. Exp Cell Res 224: 344–53

    PubMed  CAS  Google Scholar 

  118. Kasai S, Aimura H, Nishida M, Suyama T (1985) Proteolytic cleavage of single-chain pro-urokinase induces coformational change which follows activation of the zymogen and reduction of its high affinity for fibrin. J Biol Chem 260: 12377–381

    PubMed  CAS  Google Scholar 

  119. Keijer J, Linders M, Wegman JJ, et al. (1991) On the target specificity of plasminogen activator inhibitor-1: the role of heparin, vitronectin and the reactive site. Blood 78: 1254–61

    PubMed  CAS  Google Scholar 

  120. Kielberg V, Andreasen PA, Grondahl Hansen J, et al. (1985) Proenzyme to urokinase-type plasminogen activator in the mouse in vivo. FEBS Lett 182: 441–5

    PubMed  CAS  Google Scholar 

  121. Kirschke H (1998) Lysosomal cysteine peptidases and malignant tumours. Adv Exp Med Biol 421: 253–7

    Google Scholar 

  122. Knauper V, Will H, Lopez Otin C, et al. (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271: 17124–31

    PubMed  CAS  Google Scholar 

  123. Knudsen BS, Harpel PC, Nachman RL (1987) Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells. J Clin Invest 80: 1082–9

    PubMed  CAS  Google Scholar 

  124. Kobayashi H, Moniwa N, Gotoh J, et al. (1994) Role of activated protein C in facilitating basement membrane invasion by tumor cells. Cancer Res 54: 261–7

    PubMed  CAS  Google Scholar 

  125. Kobayashi H, Ohi H, Sugimura M, et al. (1992) Inhibition of in vitro ovarian cancer cell invasion by modulation of urokinase-type plasminogen activator and cathepsin B. Cancer 52: 3610–4

    CAS  Google Scholar 

  126. Kobayashi H, Schmitt M, Goretzki L, et al. (1991) Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (pro-uPA). J Biol Chem 266: 5147–52

    PubMed  CAS  Google Scholar 

  127. Konkle BA, Ginsburg D (1988) The addition of endothelial cell growth factor and heparin to human umbilical vein endothelial cell cultures decreases plasminogen activator inhibitor 1 expression. J Clin Invest 82: 579–85

    PubMed  CAS  Google Scholar 

  128. Konkle BA, Schick PK, He X, et al. (1993) Plasminogen activator inhibitor 1 mRNA is expressed in platelets and megakaryocytes and the megakaryoblastic cell line CHRF-288. Arterioscler Thromb 13: 669–74

    PubMed  CAS  Google Scholar 

  129. Kono S, Rao JS, Brunner JM, Sawaya R (1994) Immunohistochemical localization of plasminogen activator inhibitor type-1in human brain tumors. J Neuropathol Exp Neurol 53: 256–62

    PubMed  CAS  Google Scholar 

  130. Krishnamurti C, Alving BM (1992) Plasminogen activator inhibitor type 1: biochemistry and evidence for modulation of fibrinolysis in vivo. Semin Thromb Haemost 18: 67–80

    CAS  Google Scholar 

  131. Kristensen P, Pyke C, Lund LR, et al. (1990) Plasminogen activator inhibitor type-1in Lewis lung carcinoma. Histochemistry 93: 559–66

    PubMed  CAS  Google Scholar 

  132. Kruithof EK (1988) Plasminogen activator inhibitors. (a review) Enzyme 40: 113–21

    PubMed  CAS  Google Scholar 

  133. Kruithof EK, Baker MS, Bunn CL (1995) Biological and clinical aspects of plasminogen activator inhibitor type-2. Blood 86: 4007–24

    PubMed  CAS  Google Scholar 

  134. Kruithof EK, Gudinchet A, Bachmann F (1988) Plasminogen activator inhibitor 1 and plasminogen activator inhibitor-2 disease states. Thromb Haemost 59: 7–12

    PubMed  CAS  Google Scholar 

  135. Kuhn W, Pache L, Schmaldeldt B, et al. (1994) Urokinase (uPA) and PAI1 predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum-based chemotherapy. Gynecol Oncol 55: 401–9

    PubMed  CAS  Google Scholar 

  136. Lambers JW, Cammenga M, Konig BW, et al. (1987) Activation of human endothelial cell-type plasminogen activator inhibitor (PAI1) by negatively charged phosphilipids. J Biol Chem 262: 17492–6

    PubMed  CAS  Google Scholar 

  137. Lawrence DA, Olson ST, Palaniappan S, Ginsburg D (1994) Serpin reactive center loop mobility is required for inhibitor function but not for enzyme recognization. J Biol Chem 269: 27657–62

    PubMed  CAS  Google Scholar 

  138. Levin EG, Sanell L (1987) Association of a plasminogen activator inhibitor (PAI1) with the growth substratum and membrane of human endotheial cells. J Cell Biol 105: 2543–9

    PubMed  CAS  Google Scholar 

  139. Li Y, Rizvi SM, Ranson M, Allen BJ (2002) 213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model. Br. J Cancer 86: 1197–203

    PubMed  CAS  Google Scholar 

  140. Lijnen HR (1996) Pathophysiology of the plasminogen/plasmin system. Inter J Clin & Lab Res 26: 1–6

    CAS  Google Scholar 

  141. Lillis AP, Mikhailenko I, Strickland DK (2005) Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability. J Thromb Haemost 3: 1884–93

    PubMed  CAS  Google Scholar 

  142. Lin MT, Kuo IH, Chang CC, et al. (2008) Involvement of hypoxia-inducing factor-1alpha-dependent plasminogen activator inhibitor 1 up-regulation in Cyr61/CCN1-induced gastric cancer cell invasion. J Biol Chem 283(23): 15807–15

    PubMed  CAS  Google Scholar 

  143. Lindahl TL, Sigurdardottir O, Wiman B (1989) Stability of plasminogen activator inhibitor 1 (PAI1). Thromb Haemost 62: 748–51

    PubMed  CAS  Google Scholar 

  144. Liotta LA, Stetler Stevenson WG, Steeg PS (1991) Cancer invasion and metastasis: positive and negative regulatory elements. Cancer Invest 9: 543–51

    PubMed  CAS  Google Scholar 

  145. Liu D, Aguirre Ghiso J, Estrada Y, Ossowski L (2002) EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 1: 445–57

    PubMed  CAS  Google Scholar 

  146. Liu GH, Shuman MA, Cohen RL (1995) Co-expression of urokinase, urokinase receptor and PAI1 necessary for optimum invasiveness of cultured lung cancer cells. Int J Cancer 60: 501–6

    PubMed  CAS  Google Scholar 

  147. Look M, van Putten W, Duffy M, et al. (2003) Pooled analysis of prognostic impact of uPA and PAI1 in breast cancer patients. Thromb Haemost 90(3): 538–48

    PubMed  CAS  Google Scholar 

  148. Look MP (2000) Pooled analysis of uPA and PAI1 for prognosis in primary breast cancer patients. EORTC Receptor and Biomarker Study Group. Int J Biol Markers 15(1): 70–2

    PubMed  CAS  Google Scholar 

  149. Look MP, van Putten WL, Duffy MJ, et al. (2002) Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI1 in 8377 breast cancer patients. J Natl Cancer Inst 94(2): 116–28

    PubMed  CAS  Google Scholar 

  150. López-Otín C, Matrisian LM (2007) Emerging roles of proteases in tumour suppression. Nat Rev Cancer 7(10): 800–8

    PubMed  Google Scholar 

  151. Lund LR, Green KA, Stoop AA, et al. (2006) Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J 25: 2686–97

    PubMed  CAS  Google Scholar 

  152. Lyons RM, Gentry LE, Purchio AF, Moses HL (1990) Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J Cell Biol 110: 1361–7

    PubMed  CAS  Google Scholar 

  153. Martin PM, Ouafik LH (2008) Les cibles du stroma et du système angiogénique In: Le concept de cible en cancérologie. Coordinateur E. Raymond p 90–115 ed. John Libbey Eurotext, Thérapie ciblée des cancers

  154. Mawatari M, Okamura K, Matsuda T, et al. (1991) Tumor necrosis factor and epidermal growth factor modulate migration of human microvascular endothelial cells and production of tissue-type plasminogen activator and its inhibitor. Exp Cell Res 192: 574–80

    PubMed  CAS  Google Scholar 

  155. Mazzieri R, Masiero L, Zanetta L, et al. (1997) Control of type-4 collegenase activity by components of the urokinase-plasmin system: a regulatory mechanism with cell-bound reactants. EMBO Journal 16: 2319–32

    PubMed  CAS  Google Scholar 

  156. Meijer-van Gelder ME, Look MP, Peters HA, et al. (2004) Urokinase-type plasminogen activator system in breast cancer: association with tamoxifen therapy in recurrent disease. Cancer Res 64: 4563–8

    PubMed  CAS  Google Scholar 

  157. Mignatti P, Rifkin DB (1996) Plasminogen activators and matrix metalloproteinases in agiogenesis (review). Enzyme & Protein 49: 117–37

    CAS  Google Scholar 

  158. Mignatti P, Robbins E, Rifkin DB (1986) Tumor invasion through the human amniotic membrane l requirement for a proteinase cascade. Cell 47: 487–98

    PubMed  CAS  Google Scholar 

  159. Mikolajczyk SD, Millar LS, Kumar A, Saedi MS (1999) Prostatic human kallikrein 2 inactivates and complexes with plasminogen activator inhibitor-1. Int J Cancer 81: 438–42

    PubMed  CAS  Google Scholar 

  160. Mimuro J, Loskutoff DJ (1989) Binding of type-1plasminogen activator inhibitor to the extracellular matrix of cultured bovine endothelial cells. J Biol Chem 264: 5058–63

    PubMed  CAS  Google Scholar 

  161. Mingers AM, Heimburger N, Zeitler P, (1997) Homozygous type-1plasminogen deficiency. Semin Thromb Hemost 23: 259–69

    PubMed  CAS  Google Scholar 

  162. Mingers AM, Philapitsch A, Zeitler P, et al. (1999) Human homozygous type-1plasminogen deficiency and ligneous conjunctivitis. APMIS 107: 63–72

    Google Scholar 

  163. Morimoto K, Mishima H, Nishida T, Otori T (1993) Role of urokinase type plasminogen activator (uPA) in corneal epithelial migration. Thromb Haemost 69: 387–91

    PubMed  CAS  Google Scholar 

  164. Mottonen J, Strand A, Symersky J, et al. (1992) Structural basis of latency in plasminogen activator inhibitor-1. Nature 355: 270–3

    PubMed  CAS  Google Scholar 

  165. Munch M, Heegard CW, Andreasen PA (1993) Introconversions between active, inert and substrate forms of denatured/refolded type 1plasminogen activator-inhibitor. Biochim Biophys Acta 1202: 29–37

    PubMed  CAS  Google Scholar 

  166. Muracciole X, Romain S, Dufour H, et al. (2002) PAI1 and EGFR expression in adult glioma tumors: toward a molecular pronostic classification. Int J Radiat Oncol Biol Phys 52: 592–8

    PubMed  CAS  Google Scholar 

  167. Murphy G, Atkinson S, Ward R, et al. (1992) The role of plasminogen activators in the regulation of connective tissue metalloproteinases. Ann N Y Acad Sci 667: 1–12

    PubMed  CAS  Google Scholar 

  168. Murphy G, Ward R, Gavrilovic J, Atkinson S (1992) Physiological mechanisms for metalloproteinase activation. Matrix Suppl 1: 224–30

    PubMed  CAS  Google Scholar 

  169. Naitoh H, Eguchi Y, Ueyama H, et al. (1995) Localization of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, 2 and plasminogen in colon cancer. Jpn J Cancer Res 86: 48–56

    PubMed  CAS  Google Scholar 

  170. Naski MC, Mawrence DA, Mosher DF, et al. (1993) Kinetics of inactivation of alpha-thrombin by plasminogen activator inhibitor-1. Comparison of the effects of native and urea-treated forms of vitronectin. J Biol Chem 268: 12367–72

    PubMed  CAS  Google Scholar 

  171. Nekarda H, Schmitt M, Ulm K, et al. (1994) Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI1 in completely resected gastric cancer. Cancer Res 54: 2900–7

    PubMed  CAS  Google Scholar 

  172. Nekarda H, Siewert JR, Schmitt M, Ulm K (1994) Tumour-associated protelytic factors uPA and PAI1 and survival in totally resected gastric cancer (Letter; comment). Lancet 343: 117

    PubMed  CAS  Google Scholar 

  173. Nguyen DH, Catling AD, Webb DJ, et al. (1999) Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator stimulated cells in an integrin-selective manner. J Cell Biol 146: 149–64

    PubMed  CAS  Google Scholar 

  174. Nielsen HJ, Christensen IJ, Brünner N, Sorensen S (1998) Association between plasma plasminogen activator inhibitor 1 and survival in colorectal cancer (comment). BMJ 317: 750–1

    Google Scholar 

  175. Nielsen HJ, Pappot H, Christensen IJ, et al. (1998) Association between plasma concentrations of plasminogen activator inhibitor 1 and survival in patients with colorectal cancer (see comments). BMJ 316: 829–30

    PubMed  CAS  Google Scholar 

  176. Ny T, Sawdey M, Lawrence D, et al. (1986) Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci USA 83: 6678–80

    Google Scholar 

  177. Nykjaer A, Gonese M, Christensen EI, et al. (1997) Recycling of the urokinase receptor upon internalization of the uPA-serpin complexes. EMBO J 16: 2610–20

    PubMed  CAS  Google Scholar 

  178. O’Reilly MS, Holmgren L, Chen C, Folkman J (1996) Angiostatin induces and sustains dormancy of human primary tumors in mice. Nature Medicine 2: 689–92

    PubMed  Google Scholar 

  179. O’Reilly MS, Holmgren L, Shing Y, et al. (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma (see comments). Cell 79: 315–28

    PubMed  Google Scholar 

  180. Okimira Y, Sato H, Seiki M, Kido H (1997) Proteolytic activation of the precursor of membrane type-1matrix metalloproteinase by human plasmin:a possible cell surface activator. FEBS Letters 402: 181–4

    Google Scholar 

  181. Olman MA, Hagood JS, Simmons WL, et al. (1999) Fibrin fragment induction of plasminogen activator inhibitor transcription is mediated by activator protein-1 through a highly conserved element. Blood 94: 2029–38

    PubMed  CAS  Google Scholar 

  182. Olson D, Pollanen J, Hoyer Hansen G, et al. (1992) Internalization of the urokinase-plasminogen activator inhibitor type 1complex is mediated by the urokinase receptor. J Biol Chem 267: 9129–33

    PubMed  CAS  Google Scholar 

  183. Ossowski L, Biegel D, Reich E (1979) Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Cell 16: 929–40

    PubMed  CAS  Google Scholar 

  184. Ossowski L, Quigley JP, Kellerman GM, Reich B (1973) Fibrinolysis associated with oncogenic transformation. Requirement of plasminogen for correlated changes in cellular morphology, colony formation in agar and cell migration. J Exp Med 138: 1056–64

    PubMed  CAS  Google Scholar 

  185. Ossowski L, Reich E (1983) Antibodies to plasminogen activator inhibit human tumor metastasis. Cell 35: 611–9

    PubMed  CAS  Google Scholar 

  186. Pannekoek H, Veerman H, Lambers H, et al. (1986) Diergaarde P, Verweij C L, van Zonneveld A J, van Mourik J A, Endothelial plasminogen activator inhibitor (PAI): a new member of the serpin gene family. EMBO J 5: 2539–44

    PubMed  CAS  Google Scholar 

  187. Pappot H, Gardsvoll H, Romer J, et al. (1995) Plasminogen activator inhibitor type-1 in cancer: therapeutic and prognostic implications. Biol Chem Hoppe Seyler 376: 259–67

    PubMed  CAS  Google Scholar 

  188. Pedersen H, Brüner N, Francis D, et al. (1994) Prognostic impact of urokinase, urokinase receptor and plasminogen activator inhibitor in squamous and large cell lung cancer tissue. Cancer Res 54: 4671–5

    PubMed  CAS  Google Scholar 

  189. Pedersen H, Grondahl-Hansen J, Francis D, et al. (1994) Urokinase and plasminogen activator inhibitors type-1 in pulmonary adenocarcinoma. Cancer Res 54: 120–3

    PubMed  CAS  Google Scholar 

  190. Pedersen N, Schmitt M, Ronne E, et al. (1993) A ligand-free, soluble urokinase receptor is present in the ascitic fluid from patients with ovarian cancer. J Clin Invest 92: 2160–7

    PubMed  CAS  Google Scholar 

  191. Petersen LC, Lund LR, Nielsen LS, et al. (1982) One chain urokinase-type plasminogen activator form human sarcoma cells is a proenzyme with little or no intrinsic activity. J Biol Chem 263: 11189–95

    Google Scholar 

  192. Peyrat JP, Vanlemmens L, Fournier J, et al. (1998) Prognostic value of p53 and urokinase-type plasminogen activator in node-negative human breast cancers. Clin Cancer Res 4(1): 189–96

    PubMed  CAS  Google Scholar 

  193. Ploug M (2003) Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor. Curr Pharm Des 9: 1499–528

    PubMed  CAS  Google Scholar 

  194. Ploug M, Ellis V, Dano K (1994) Ligand interaction between urokinase-type plasminogen activator and its receptor probed with 8-anilino-1-naphthalene sulfonate. Evidence for a hydrophobic binding site exposed only on the intact receptor. Biochemistry 33: 8991–7

    PubMed  CAS  Google Scholar 

  195. Ploug M, Ronne E, Behrendt N, et al. (1991) Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem 266: 1925–33

    Google Scholar 

  196. Pollanen J, Stephens RW, Vaheri A (1991) Directed plasminogen activation at the surface of normal and malignant cells. Adv. Cancer Res 57: 273–328

    PubMed  CAS  Google Scholar 

  197. Pollanen J, Vaheri A, Tapiovaara H, et al. (1990) Prourokinase activation on the surface of human rhabdomyosarcoma cells: localization and inactivation of newly formed urokinase-type plasminogen activator by recombinant class 2 plasminogen activator inhibitor. Proc Natl Acad Sci USA 87: 2230–4

    PubMed  CAS  Google Scholar 

  198. Preissner KT, Kanse SM, May AE (2000) Urokinase receptor: a molecular organizer in cellular communication. Curr Opin Cell Biol 12: 621–8

    PubMed  CAS  Google Scholar 

  199. Pyke C, Kristensen P, Ralfkiaer E, et al. (1991) The plasminogen activation system in human colon cancer: messenger RNA for inhibitor PAI1 is located in endothelial cells in the tumor stroma. Cancer Res 51:4067–71

    PubMed  CAS  Google Scholar 

  200. Pyke C, Kristensen P, Ralfkiaer E, et al. (1991) Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol 138: 1059–67

    PubMed  CAS  Google Scholar 

  201. Quax PH, van Muijen GN, Weening Verhoeff EJ, et al. (1991) Metastatic behavior of human melanoma cell lines in nude mice correlates with urokinase-type plasminogen activator, its type-1 inhibitor, and urokinase-mediated matrix degradation. J Cell Biol 115: 191–9

    PubMed  CAS  Google Scholar 

  202. Ragno P, Montuori N, Rossi G (1995) Urokinase-type plasminogen activator type-2 plasminogen: activator inhibitor complexes are not internalized upon binding to the urokinase-type plasminogen-activator receptor in THP-1 cells.Interaction of urokinase-type plasminogen activator/type-2 plasminogen-activator inhibitor complexes with the cell surface. Eur J Biochem 233: 514–9

    PubMed  CAS  Google Scholar 

  203. Ranson M, Andronicos NM (2003) Plasminogen binding and cancer: promises and pitfalls. Front Biosci 8: s294–s304

    PubMed  CAS  Google Scholar 

  204. Ranson M, Tian Z, Andronicos NM, et al. (2002) In vitro cytotoxicity of bismuth-213 (213Bi)-labeled-plasminogen activator inhibitor type-2 (alpha- PAI2) on human breast cancer cells. Breast Cancer Res Treat 71: 149–59

    PubMed  CAS  Google Scholar 

  205. Reilly CF, Hutzelmann JE (1992) Plasminogen activator inhibitor 1 binds to fibin and inhibits tissue-type plasminogen activator-mediated fibrin dissolution. J Biol Chem 267: 17128–35

    PubMed  CAS  Google Scholar 

  206. Resnati M, Pallavicini I, Wang JM, et al. (2002) The fibrinolytic receptor for urokinase activates the G protein coupled chemotactic receptor FPRL1/LXA4R. Proc Natl Acad Sci USA 99: 1359–64

    PubMed  CAS  Google Scholar 

  207. Rodenburg KW, Kjoller L, Petersen HH, Andreasen PA (1998) Binding of urokinase-type plasminogen activator- plasminogen activator inhibitor 1 complex to the endocytosis receptors alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein and very-low-density lipoprotein receptor involves basic residues in the inhibitor. Biochem J 329(Pt 1): 55–63

    PubMed  CAS  Google Scholar 

  208. Roldan AL, Cubellis MV, Masucci MT, et al. (1990) Cloning and expression of the receptor, a central molecule in cell surface, plasmin dependent proteolysis (published erratum appears in EMBO J 1990 9: 1674). EMBO J 9: 467–74

    PubMed  CAS  Google Scholar 

  209. Romer J, Bugge TH, Pyke C, et al. (1996) Impaired wound healing in mice with a disrupted plasminogen gene. Nat Med 2: 287–92

    PubMed  CAS  Google Scholar 

  210. Romer J, Lund LR, Eriksen J, et al. (1991) Differential expression of urokinase-type plasminogen activator and its type-1 inhibitor during healing of mouse skin wounds. J Invest Dermatol 97: 803–11

    PubMed  CAS  Google Scholar 

  211. Romer J, Pyke C, Lund LR, et al. (1994) Expression of uPA and its receptor by both neoplastic and stroma cells during xenograft invasion. Int J Cancer 57: 553–60

    PubMed  CAS  Google Scholar 

  212. Ronne E, Behrendt N, Ellis V, et al. (1991) Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor. FEBS Lett 288: 223–36

    Google Scholar 

  213. Ronne E, Pappot H, Grondahl Hansen J, et al. (1995) The receptor of urokinase plasminogen activator is present in plasma from healthy donors and elevated in patients with paroxysmal nocturnal heamoglobinuria. Br J Haemat 89: 576–81

    CAS  Google Scholar 

  214. Rosenberg S (2003) The urokinase-type plasminogen activator system in cancer and other pathological conditions: introduction and perspective. Curr Pharm Des 9(19):4p

    PubMed  Google Scholar 

  215. Rusnati M, Coltrini D, Oreste P, et al. (1997) Interaction of HIV-1 tat protein with heparin. Role of the backbone structure, sulfation and size. J Biol Chem 272: 11313–20

    PubMed  CAS  Google Scholar 

  216. Samad F, Yamamoto K, Loskutoff DJ (1996) Distribution and regulation of plasminogen activator inhibitor 1 in murine adipose tissue in vivo - induction by tumor necrosis factor-alpha and lipopolysaccharide. J Clin Invest 97: 37–46

    PubMed  CAS  Google Scholar 

  217. Sappino AP, Belin D, Huarte J, et al. (1991) Differential protease expression by cutaneous squamous and basal cell carcinomas. J Clin Invest 88: 1073–9

    PubMed  CAS  Google Scholar 

  218. Sappino AP, Huarte J, Belin D, Vassali JD (1989) Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos. J Cell Biol 109: 2471–9

    PubMed  CAS  Google Scholar 

  219. Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta1-like molecule by plasmin during co-culture. J Cell Biol 109: 309–15

    PubMed  CAS  Google Scholar 

  220. Schmitt M, Harbeck N, Thomssen C, et al. (1997) Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost 78(1): 285–96

    PubMed  CAS  Google Scholar 

  221. Schousboe I, Feddersen K, Rojkjaer R (1999) Factor XIIa is a kinetically favorable plasminogen activator (in process citation). Thromb Haemost 82: 1041–6

    PubMed  CAS  Google Scholar 

  222. Schuster V, Mingers AM, Seidenspinner S, et al. (1997) Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. Blood 90: 958–66

    PubMed  CAS  Google Scholar 

  223. Schuster V, Seidenspinner S, Zeitler P, et al. (1999) Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. Blood 93: 3457–66

    PubMed  CAS  Google Scholar 

  224. Seiffert D, Loskutoff DJ (1991) Kinetic analysis of the interaction between type 1 plasminogen activator inhibitor and vitronectin and evidence that the bovine inhibitor binds to a thrombin-derived amino-terminal fragment of bovine vitronectin. Biochim. Biophys. Acta 1078: 23–30

    PubMed  CAS  Google Scholar 

  225. Shapiro RL, Duquette JG, Roses DF, et al. (1996) Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals. Cancer Res 56: 3597–604

    PubMed  CAS  Google Scholar 

  226. Sier CF, Vloedgraven HJ, Ganesh S, et al. (1994) Inactive urokinase and increased levels of its inhibitor type 1 in colorectal cancer liver metastasis. Gastroenterology 107: 1449–56

    PubMed  CAS  Google Scholar 

  227. Sim PS, Fayle DR, Doe WF, Stephens RW (1986) Monoclonal antibodies inhibitory to human plasmin. Definitive demonstration of a role for plasmin in activating the proenzyme of urokinase-type plasminogen activator. Eur J Biochem 158: 537–42

    PubMed  CAS  Google Scholar 

  228. Simpson AJ, Booth NA, Moore NR, Benett B (1991) Distribution of plasminogen activator inhibitor (PAI1) in tissues. J Clin Pathol 44: 139–43

    PubMed  CAS  Google Scholar 

  229. Skeldal S, Larsen JV, Pedersen KE, et al. (2006) Binding areas of urokinase-type plasminogen activator-plasminogen activator inhibitor 1 complex for endocytosis receptors of the low-density lipoprotein receptor family, determined by site-directed mutagenesis. FEBS J 273(22): 5143–59

    PubMed  CAS  Google Scholar 

  230. Slivka SR, Loskutoff DJ (1991) Platelets stimulate endothelial cells to synthetize type 1 plasminogen activator inhibitor. Evaluation of the role of transforming growth factor beta. Blood 77: 1013–9

    PubMed  CAS  Google Scholar 

  231. Soff GA, Sanderowitz J, Gately S, et al. (1995) Expression of plasminogen activator inhibitor type-1 by human prostate carcinoma cells inhibits primary tumor growth, turner-associated angiogenesis, and metastatis to lung and liver in an athymic mouse model. J Clin Invest 96: 2593–600

    PubMed  CAS  Google Scholar 

  232. Solberg H, Romer J, Brünner N, et al. (1994) A cleaved form of the receptor for urokinase-type plasminogen activator in invasive transplanted human and murine tumors. Int J Cancer 58: 877–81

    PubMed  CAS  Google Scholar 

  233. Sordat B, Reiter L, Cajot JF (1990) Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type 1 plasminogen activator inhibitor. Cell Differ. Dev 32: 277–85

    PubMed  CAS  Google Scholar 

  234. Sprengers ED, Akkerman JW, Jansen BG (1986) Blood platelet plasminogen activator inhibitor: two different pools of endothelial cell type plasminogen activator inhibitor in human blood. Thromb Haemost 55: 325–9

    PubMed  CAS  Google Scholar 

  235. Spyratos F, Bouchet C, Tozlu S, et al. (2002) Prognostic value of uPA, PAI1 and PAI2 mRNA expression in primary breast cancer. Anticancer Res 22: 2997–3003

    PubMed  CAS  Google Scholar 

  236. Spyratos F, Martin PM, Hacène K, et al. (1992) Multiparametric prognostic evaluation of biological factors in primary breast cancer. J Natl Cancer Inst 84: 1266–71

    PubMed  CAS  Google Scholar 

  237. Stahl A, Mueller BM (1997) Melanoma cell migration on vitronectin: regulation by components of the plasminogen activation system. Int J Cancer 71: 116–22

    PubMed  CAS  Google Scholar 

  238. Stefansson S, McMahon GA, Petitclerc E, Lawrence DA (2003) Plasminogen activator inhibitor 1 in tumor growth, angiogenesis and vascular remodeling. Curr Pharm Des 9: 1545–64

    PubMed  CAS  Google Scholar 

  239. Stefansson S, Muhammad S, Cheng XF, et al. (1998) Plasminogen activator inhibitor 1 contains a cryptic high affinity binding site for the low density lipoprotein receptor related protein. J Biol Chem 273: 6358–66

    PubMed  CAS  Google Scholar 

  240. Stephens RW, Golder JP (1984) Novel properties of human monocyte plasminogen activator. Eur J Biochem 139: 253–8

    PubMed  CAS  Google Scholar 

  241. Stephens RW, Golder JP, Fayle DR, et al. (1985) Minactivin expression in human monocyte and macrophage populations. Blood 66: 333–7

    PubMed  CAS  Google Scholar 

  242. Stephens RW, Nielsen HJ, Christensen IJ, et al. (1999) Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis. J Natl Cancer Inst 91: 869–74

    PubMed  CAS  Google Scholar 

  243. Stephens RW, Pedersen AN, Nielsen HJ, et al. (1997) ELISA determination of soluble urokinase receptor in blood from healthy donors and cancer patients. Clin Chem 43: 1868–76

    PubMed  CAS  Google Scholar 

  244. Stephens RW, Pellanen J, Tapiovaara H, et al. (1989) Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants. J Cell Biol 108: 1987–95

    PubMed  CAS  Google Scholar 

  245. Strickland DK, Gonias SL, Argraves WS (2002) Diverse roles for the LDL receptor family. Trends Endocrinol Metab 13: 66–74

    PubMed  CAS  Google Scholar 

  246. Strickland S, Richards WG (1992) Invasion of the trophoblasts. Cell 71: 355–

    PubMed  CAS  Google Scholar 

  247. Stutchbury TK, Al-ejeh F, Stillfried GE, et al. (2007) Preclinical evaluation of 213Bi-labeled plasminogen activator inhibitor type-2 in an orthotopic murine xenogenic model of human breast carcinoma. Mol. Cancer Ther 6: 203–12

    PubMed  CAS  Google Scholar 

  248. Sumiyoshi K, Baba S, Sakaguchi S, et al. (1991) Increase in levels of plasminogen activator and type 1 plasminogen activator inhibitor in human breast cancer: possible roles in tumor progression and metastasis. Thromb Res 63: 59–71

    PubMed  CAS  Google Scholar 

  249. Sumiyoshi K, Serikawa K, Urano T, et al. (1992) Plasminogen activator system in human breast cancer. Int J Cancer 50: 345–8

    PubMed  CAS  Google Scholar 

  250. Sweep CG, Geurts-Moespot J, Grebenschikov N, et al. (1998) External quality assessment of trans-European multicentre antigen determinations (enzyme-linked immunosorbent assay) of urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI1) in human breast cancer tissue extracts. Br J Cancer 78(11): 1434–41

    PubMed  CAS  Google Scholar 

  251. Thornton AJ, Gelehrter TD (1995) Human hepatocytes express the gene for type 1 plasminogen activator inhibitor (PAI1) in vivo. Fibrinolysis 9: 9–15

    CAS  Google Scholar 

  252. Thorsen S, Philips M, Selmer J, et al. (1988) Kinetics of inhibition of tissue-type and urokinase-type plasminogen activator by plasminogen-activator inhibitor type 1 and type-2. Europ J Biochem 175: 33–9

    PubMed  CAS  Google Scholar 

  253. Tsuchiya H, Katsuo S, Matsuda E, et al. (1995) The antibody to plasminogen activator inhibitor 1 suppresses pulmonary metastases of human fibrosarcoma in athymic mice. Gen Diagn Pathol 141: 41–8

    PubMed  CAS  Google Scholar 

  254. Uddhammar A, Rantapaa Dahlqvist S, Nilsson TK (1992) Plasminogen activator inhibitor and von Willebrand factor in polymyalgia rheumatica. Clin Rheumatol 11: 211–5

    PubMed  CAS  Google Scholar 

  255. Umeda T, Eguchi Y, Okino K, et al. (1997) Cellular localization of urokinase-type plasminogen activator, its inhibitors, and their mRNAs in breast cancer tissues. J Pathol 183: 388–397

    PubMed  CAS  Google Scholar 

  256. Urano T, Strandberg L, Johansson LB, Ny T (1992) A substrate-like form of plasminogen-activator-inhibitor type 1. Conversions between different forms by sodium dodecyl sulphate. Eur J Biochem 209: 985–92

    PubMed  CAS  Google Scholar 

  257. Vanmeijer M, Pannekoek H (1995) Structure of plasminogen activator inhibitor 1 (PAI1) and its function in fibrinolysis: an update (review). Fibrinolysis 9: 263–76

    CAS  Google Scholar 

  258. Vassali JD, Baccino D, Belin DA (1985) Cellular binding site for the Mr 55,00 form of the human plasminogen activator, urokinase. J Cell Biol 100: 86–92

    Google Scholar 

  259. Vavani J, Orr W, Ward PA (1979) Cell-associated proteases affect tumour cell migration in vitro. J Cell Sci 26: 241–52

    Google Scholar 

  260. Vontempelhoff GF, Heilmann L, Dietrich M, et al. (1997) Plasmatic plasminogen activator inhibitor activity in patients with primary breast cancer. Thromb Haemat 77: 606–8

    CAS  Google Scholar 

  261. Wagner SN, Atkinson MJ, Thanner S, et al. (1995) Modulation of urokinase and urokinase receptor gene expression in human renal cell carcinoma. Am J Pathol 147: 183–92

    PubMed  CAS  Google Scholar 

  262. Waltz DA, Chapman HA (1994) Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy. J Biol Chem 269: 14746–50

    PubMed  CAS  Google Scholar 

  263. Waltz DA, Sailor LZ, Chapman HA (1993) Cytokines induce urokinase-dependent adhesion of human myeloid cells. A regulatory role for plasminogen activator inhibitors. J Clin Invest 91: 1541–52

    PubMed  CAS  Google Scholar 

  264. Webb DJ, Nguyen DH, Gonias SL (2000) Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion. J. Cell Sci 113(Pt 1): 123–34

    PubMed  CAS  Google Scholar 

  265. Webb DJ, Thomas KS, Gonias SL (2001) Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signaling and thereby promotes MCF-7 cell growth. J Cell Biol 152: 741–52

    PubMed  CAS  Google Scholar 

  266. Wei Y, Lukashev M, Simon DI, et al. (1996) Regulation of integrin function by the urokinase receptor. Science 273: 1551–5

    PubMed  CAS  Google Scholar 

  267. Wei Y, Waltz DA, Rao N (1994) Identification of the urokinase receptor as all adhesion receptor for vitronectin. J Biol Chem 269: 32380–8

    PubMed  CAS  Google Scholar 

  268. Wei Y, Yang X, Liu Q, et al. (1999) A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling. J Cell Biol 144: 1285–94

    PubMed  CAS  Google Scholar 

  269. Whisstock JC, Bottomley SP (2006) Molecular gymnastics: serpin structure, folding and misfolding. Curr Opin Struct Biol 16: 761–8

    PubMed  CAS  Google Scholar 

  270. Wilhelm O, Schmitt M, Hohl S, Senekowitsch R, et al. (1995) Antisense inhibition of urokinase reduces spread of human ovarian cancer in mice. Clin Exp Metastasis 13: 296–302

    PubMed  CAS  Google Scholar 

  271. Wohlwend A, Belin D, Vassalli JD (1987) Plasminogen activator-specific inhibitors in mouse acrophages: in vivo and in vitro modulation of their synthesis and secretion. J Immunol 139: 1278–84

    PubMed  CAS  Google Scholar 

  272. Wun TC, Ossowski L, Reich E (1982) A proenzyme form of human urokinase. J Biol Chem 257: 7262–8

    PubMed  CAS  Google Scholar 

  273. Yamamoto M, Sawaya R, Mohanam S, et al. (1994) Expression and cellular localization of messenger RNA for plasminogen activator inhibitor type 1 in human astrocytomas in vivo. Cancer Res 54: 3329–32

    PubMed  CAS  Google Scholar 

  274. Yoshida E, Ohmura S, Sugiki M, et al. (1995) Prostate-specific antigen activates single-chain urokinase-type plasminogen activator. Int J Cancer 63: 863–5

    PubMed  CAS  Google Scholar 

  275. Zeng ZS, Guillem JG (1995) Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastases. Br J Cancer 72: 575–82

    PubMed  CAS  Google Scholar 

  276. Zheng MH, Fan Y, Panicker A, et al. (1995) Detection of mRNAs for urokinase-type plasminogen activator, its receptor, and type 1 inhibitor in giant cell tumors with in situ hybridization. Am J Patjol 147: 1559–66

    CAS  Google Scholar 

  277. Hayes DF, Bast RC, Desch CE, et al. (1996) Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 88(20):1456–66

    PubMed  CAS  Google Scholar 

  278. Harris L, Fritsche H, Mennel R, et al. (2007) American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25(33):5287–312

    PubMed  CAS  Google Scholar 

  279. Sturgeon CM, Hoffman BR, Chan DW, et al. (2008) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice: quality requirements. Clin Chem 54(8):e1–e10

    Google Scholar 

  280. Sturgeon CM, Duffy MJ, Stenman UH, et al. (2008) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 54(12):e11–79

    PubMed  CAS  Google Scholar 

  281. Luporsi E, André F, Bellocq JP et al. (2009) « Place des biomarqueurs dans la prise en charge du cancer du sein - Rapport 2009 sur l’état des connaissances relatives aux biomarqueurs tissulaires uPA/PAI-1, Oncotype DX™ et MammaPrint®. Collection « Rapports & synthèses » Institut National du Cancer (INCa), Société française de sénologie et de pathologie mammaire (SFSPM)

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Martin, PM., Dussert, C., Romain, S. et al. Relations du système plasminogène-plasmine et cancer. Oncologie 12, 322–340 (2010). https://doi.org/10.1007/s10269-010-1893-8

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