Pathophysiologic significance of procoagulant microvesicles in cancer disease and progression

 

 Buy Article Permissions and Reprints

Summary

Microvesicles (MV) are submicrometric membrane fragments (0.1 to 1 μm), released from the plasma membrane of activated or apoptotic cells. They are characterized by most of the antigenic profile of the cells they originate from, and by the presence of procoagulant phospholipids at their surface. MV are detectable in the peripheral blood of mammals and considered as efficient effectors in the haemostatic or thrombotic responses, able to remotely initiate or amplify beneficial or deleterious processes, depending on the circumstances. Variations in their level and pheno-type make them relevant pathogenic markers of thrombotic disorders and vascular damage. To date, MV are recognized as mediators of communication allowing cells to influence a target present in the local microenvironment as well as to at distant sites. The mechanisms by which MV interact with target cells are still unclear, but a number of studies suggest involvement of MV-cell fusion or ligand-receptor interactions. More importantly, MV have been shown implicated in horizontal transfer of genetic material. This review focuses on the role of MV in the context of cancer, and their possible part in cancer associated thrombosis.

• References

• 1 Abid Hussein MN, Böing AN, Biró E. et al. Phospholipid composition of in vitro endothelial microparticles and their in vivo thrombogenic properties. Thromb Res 2008; 121: 865-871.
  CrossrefPubMedGoogle Scholar
• 2 Afshar-Kharghan V, Thiagarajan P. Leukocyte adhesion and thrombosis. Curr Opin Hematol 2006; 13: 34-39.
  CrossrefPubMedGoogle Scholar
• 3 Al-Nedawi K, Meehan B, Micallef J. et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 2008; 10: 619-624.
  CrossrefPubMedGoogle Scholar
• 4 Andreola G, Rivoltini L, Castelli C. et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 2002; 195: 1303-1316.
  CrossrefPubMedGoogle Scholar
• 5 Angelucci A, D’Ascenzo S, Festuccia C. et al. Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines. Clin Exp Metastasis 2000; 18: 163-170.
  CrossrefPubMedGoogle Scholar
• 6 Baj-Krzyworzeka M, Szatanek R, Weglarczyk K. et al. Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 2006; 55: 808-818.
  CrossrefPubMedGoogle Scholar
• 7 Baj-Krzyworzeka M, Szatanek R, Weglarczyk K. et al. Tumour-derived microvesicles modulate biological activity of human monocytes. Immunol Lett 2007; 113: 76-82.
  CrossrefPubMedGoogle Scholar
• 8 Bassé F, Gaffet P, Rendu F, Bienvenüe A. Translocation of spin-labeled phospholipids through plasma membrane during thrombin- and ionophore A23187-induced platelet activation. Biochemistry 1993; 32: 2337-2344.
  CrossrefPubMedGoogle Scholar
• 9 Belting M, Dorrell MI, Sandgren S. et al. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nat Med 2004; 10: 502-509.
  CrossrefPubMedGoogle Scholar
• 10 Bergsmedh A, Szeles A, Henriksson M. et al. Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 2001; 98: 6407-6411.
  CrossrefPubMedGoogle Scholar
• 11 Boucharaba A, Serre CM, Grès S. et al. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 2004; 114: 1714-1725.
  CrossrefPubMedGoogle Scholar
• 12 Brill A, Dashevsky O, Rivo J. et al. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 2005; 67: 30-38.
  CrossrefPubMedGoogle Scholar
• 13 Camerer E, Gjernes E, Wiiger M. et al. Binding of factor VIIa to tissue factor on keratinocytes induces gene expression. J Biol Chem 2000; 275: 6580-6585.
  CrossrefPubMedGoogle Scholar
• 14 Castellana D, Zobairi F, Martinez MC. et al. Membrane microvesicles as actors in the establishment of a favorable prostatic tumoral niche: A role for activated fibroblasts and CX3CL1-CX3CR1 axis. Cancer Res. 2009 in press.
  PubMedGoogle Scholar
• 15 Cornwell MM, Gottesman MM, Pastan IH. Increased vinblastine binding to membrane vesicles from multidrug-resistant KB cells. J Biol Chem 1986; 261: 7921-7928.
  PubMedGoogle Scholar
• 16 De la Taille A, Chen MW, Burchardt M. et al. Apoptotic conversion: evidence for exchange of genetic information between prostate cancer cells mediated by apoptosis. Cancer Res 1999; 59: 5461-5463.
  PubMedGoogle Scholar
• 17 Del Conde I, Shrimpton CN, Thiagarajan P, López JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005; 106: 1604-1611.
  CrossrefPubMedGoogle Scholar
• 18 Del Conde I, Bharwani LD, Dietzen DJ. et al. Microvesicle-associated tissue factor and Trousseau‘s syndrome. J Thromb Haemost 2007; 5: 70-74.
  CrossrefPubMedGoogle Scholar
• 19 Deregibus MC, Cantaluppi V, Calogero R. et al. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007; 110: 2440-2448.
  CrossrefPubMedGoogle Scholar
• 20 Dvorak FH, Rickles FR. Malignancy and hemostasis. In: Coleman RB, Marder VJ, Clowes AW. et al (eds). Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia: Lippincott Williams & Wilkins; 2006: 851-873.
  Google Scholar
• 21 Fernandes RS, Kirszberg C, Rumjanek VM, Monteiro RQ. On the molecular mechanisms for the highly procoagulant pattern of C6 glioma cells. J Thromb Haemost 2006; 4: 1546-1552.
  CrossrefPubMedGoogle Scholar
• 22 Freyssinet JM. Cellular microparticles: what are they bad or good for?. J Thromb Haemost 2003; 1: 1655-1662.
  CrossrefPubMedGoogle Scholar
• 23 Ginestra A, La Placa MD, Saladino F. et al. The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness. Anticancer Res 1998; 18: 3433-3437.
  PubMedGoogle Scholar
• 24 Hegmans JP, Bard MP, Hemmes A. et al. Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol 2004; 164: 1807-1815.
  CrossrefPubMedGoogle Scholar
• 25 Holmgren L, Szeles A, Rajnavölgyi E. et al. Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood 1999; 93: 3956-3963.
  PubMedGoogle Scholar
• 26 Hron G, Kollars M, Weber H. et al. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 2007; 97: 119-123.
  Article in Thieme ConnectPubMedGoogle Scholar
• 27 Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM. Membrane microparticles: two sides of the coin. Physiology (Bethesda) 2005; 20: 22-27.
  CrossrefPubMedGoogle Scholar
• 28 Iero M, Valenti R, Huber V. et al. Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 2008; 15: 80-88.
  CrossrefPubMedGoogle Scholar
• 29 Kanazawa S, Nomura S, Kuwana M. et al. Monocyte-derived microparticles may be a sign of vascular complication in patients with lung cancer. Lung Cancer 2003; 39: 145-149.
  CrossrefPubMedGoogle Scholar
• 30 Kerbel RS, Kobayashi H, Graham CH. Intrinsic or acquired drug resistance and metastasis: are they linked phenotypes?. J Cell Biochem 1994; 56: 37-47.
  CrossrefPubMedGoogle Scholar
• 31 Kim CW, Lee HM, Lee TH. et al. Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res 2002; 62: 6312-6317.
  PubMedGoogle Scholar
• 32 Kim HK, Song KS, Park YS. et al. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastatic predictor. Eur J Cancer 2003; 39: 184-191.
  CrossrefPubMedGoogle Scholar
• 33 Kim HK, Song KS, Chung JH. et al. Platelet micro-particles induce angiogenesis in vitro. Br J Haematol 2004; 124: 376-384.
  CrossrefPubMedGoogle Scholar
• 34 Kim JW, Wieckowski E, Taylor DD. et al. Fas ligandpositive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res 2005; 11: 1010-1020.
  PubMedGoogle Scholar
• 35 Janowska-Wieczorek A, Wysoczynski M, Kijowski J. et al. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 2005; 113: 752-760.
  CrossrefPubMedGoogle Scholar
• 36 Liu C, Yu S, Zinn K. et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol 2006; 176: 1375-1385.
  CrossrefPubMedGoogle Scholar
• 37 Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol 2005; 205: 275-292.
  CrossrefPubMedGoogle Scholar
• 38 López JA, Kearon C, Lee AY. Deep venous thrombosis. Hematology Am Soc Hematol Educ Program 2004; 439-456.
  PubMedGoogle Scholar
• 39 Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 2007; 27: 1687-1693.
  CrossrefPubMedGoogle Scholar
• 40 Mallat Z, Hugel B, Ohan J. et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-353.
  CrossrefPubMedGoogle Scholar
• 41 Martínez M, Larbret F, Zobairi F. et al. Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood 2006; 108: 3012-3020.
  CrossrefPubMedGoogle Scholar
• 42 Mezentsev A, Merks RM, O’Riordan E. et al. Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. Am J Physiol Heart Circ Physiol 2005; 289: H1106-H1114.
  CrossrefPubMedGoogle Scholar
• 43 Miller GJ, Bauer KA, Howarth DJ. et al. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway. J Thromb Haemost 2004; 2: 2107-2114.
  CrossrefPubMedGoogle Scholar
• 44 Millimaggi D, Mari M, D’Ascenzo S. et al. Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia 2007; 9: 349-357.
  CrossrefPubMedGoogle Scholar
• 45 Milsom C, Yu J, May L. et al. Diverse roles of tissue factor-expressing cell subsets in tumor progression. Semin Thromb Hemost 2008; 34: 170-181.
  Article in Thieme ConnectPubMedGoogle Scholar
• 46 Morel O, Toti F, Hugel B. et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26: 2594-2604.
  CrossrefPubMedGoogle Scholar
• 47 Niemetz J, Fallon JT, Harrington E, Hathcock J. Rapid generation of thrombin by atheroma and platelets. J Thromb Haemost 2004; 2: 321-326.
  CrossrefPubMedGoogle Scholar
• 48 Ogura H, Tanaka H, Koh T. et al. Enhanced production of endothelial microparticles with increased binding to leukocytes in patients with severe systemic inflammatory response syndrome. J Trauma 2004; 56: 823-830.
  CrossrefPubMedGoogle Scholar
• 49 Pasca di Magliano M, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 2003; 3: 903-911.
  CrossrefPubMedGoogle Scholar
• 50 Periard D, Boulanger CM, Eyer S. et al. Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke?. Stroke 2007; 38: 1636-1638.
  CrossrefPubMedGoogle Scholar
• 51 Rak J, Yu JL, Luyendyk J, Mackman N. Onco-genes, Trousseau syndrome, and cancer-related changes in the coagulome of mice and humans. Cancer Res 2006; 66: 10643-10646.
  CrossrefPubMedGoogle Scholar
• 52 Rak J, Milsom C, Yu J. Tissue factor in cancer. Curr Opin Hematol 2008; 15: 522-528.
  CrossrefPubMedGoogle Scholar
• 53 Ran S, Thorpe PE. Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy. Int J Radiat Oncol Biol Phys 2002; 54: 1479-1484.
  CrossrefPubMedGoogle Scholar
• 54 Ratajczak J, Miekus K, Kucia M. et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006; 20: 847-856.
  CrossrefPubMedGoogle Scholar
• 55 Rauch U, Antoniak S. Tissue factor-positive microparticles in blood associated with coagulopathy in cancer. Thromb Haemost 2007; 97: 9-10.
  Article in Thieme ConnectPubMedGoogle Scholar
• 56 Rickles FR. Mechanisms of cancer-induced thrombosis in cancer. Pathophysiol Haemost Thromb 2006; 35: 103-110.
  CrossrefPubMedGoogle Scholar
• 57 Ruf W. Redundant signaling of tissue factor and thrombin in cancer progression?. J Thromb Haemost 2007; 5: 1584-1587.
  CrossrefPubMedGoogle Scholar
• 58 Salzer U, Hinterdorfer P, Hunger U. et al. Ca²⁺-dependent vesicle release from erythrocytes involves stomatin-specific lipid rafts, synexin (annexin VII), and sorcin. Blood 2002; 99: 2569-2577.
  CrossrefPubMedGoogle Scholar
• 59 Satta N, Toti F, Feugeas O. et al. Monocyte vesiculation: A mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules following stimulation by lipopolysaccharide. J Immunol 1994; 153: 3245-3255.
  PubMedGoogle Scholar
• 60 Shedden K, Xie XT, Chandaroy P. et al. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 2003; 63: 4331-4337.
  PubMedGoogle Scholar
• 61 Sidhu SS, Mengistab AT, Tauscher AN. et al. The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions. Oncogene 2004; 23: 956-963.
  CrossrefPubMedGoogle Scholar
• 62 Spetz AL, Patterson BK, Lore K. et al. Functional gene transfer of HIV DNA by an HIV receptor-independent mechanism. J Immunol 1999; 163: 736-742.
  PubMedGoogle Scholar
• 63 Tabibzadeh SS, Kong QF, Kapur S. Passive acquisition of leukocyte proteins is associated with changes in phosphorylation of cellular proteins and cell-cell adhesion properties. Am J Pathol 1994; 145: 930-940.
  PubMedGoogle Scholar
• 64 Taraboletti G, D’Ascenzo S, Borsotti P. et al. Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol 2002; 160: 673-680.
  CrossrefPubMedGoogle Scholar
• 65 Taylor DD, Gerçel-Taylor C. Tumour-derived exo -somes and their role in cancerassociated T-cell signalling defects. Br J Cancer 2005; 92: 305-311.
  CrossrefPubMedGoogle Scholar
• 66 Tesselaar ME, Romijn FP, Van Der Linden IK. et al. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?. J Thromb Haemost 2007; 5: 520-527.
  CrossrefPubMedGoogle Scholar
• 67 Valenti R, Huber V, Filipazzi P. et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with TGF-α-mediated suppressive activity on T lymphocytes. Cancer Res 2006; 66: 9290-9298.
  CrossrefPubMedGoogle Scholar
• 68 VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59: 277-287.
  CrossrefPubMedGoogle Scholar
• 69 Yu JL, Rak JW. Shedding of tissue factor (TF)-containing microparticles rather than alternatively spliced TF is the main source of TF activity released from human cancer cells. J Thromb Haemost 2004; 2: 2065-2067.
  CrossrefPubMedGoogle Scholar
• 70 Yu JL, May L, Lhotak V. et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 2005; 105: 1734-1741.
  CrossrefPubMedGoogle Scholar
• 71 Zacharski LR. Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy. Cancer Lett 2002; 186: 1-9.
  CrossrefPubMedGoogle Scholar
• 72 Zhang Y, Deng Y, Luther T. et al. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest 1994; 94: 1320-1327.
  CrossrefPubMedGoogle Scholar
• 73 Zwaal RF, Comfurius P, Bevers EM. Mechanism and function of changes in membrane-phospholipid asymmetry in platelets and erythrocytes. Biochem Soc Trans 1993; 21: 248-253.
  CrossrefPubMedGoogle Scholar
• 74 Zwicker JI, Furie BC, Furie B. Cancer-associated thrombosis. Crit Rev Oncol Hematol 2007; 62: 126-136.
  CrossrefPubMedGoogle Scholar