Skip to main content
Log in

Tumor invasion and host extracellular matrix

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Summary

In this review some of the major mechanistic pathways by which tumor cells are thought to invade host tissues are discussed. Tumor invasion has been conceived to be the result of pathological, close-range interactions between malignant cells and host stroma. The sequence of events that characterize invasion can be summarized as follows: (a) Tumor cell clusters break from the confinement of the primary tumor. Loss of intercellular junctions (desmosomes), alterations in the chemical composition and physical properties of the cell surface coat (loss of fibronectin and heparan sulfate; excessive amounts of hyaluronate), and loosening of cell-substrate interactions (loss of hemidesmosomes, fibronectin, and heparan sulfate), are among the most frequently listed causes of tumor cell shedding. (b) Increased proteolytic activities at the invasion front cause focal alterations in the surrounding extracellular matrix, thereby changing its physical properties. Collagenases and cathepsins, as well as elastase and other neutral proteinases are the enzymes most frequently associated with matrix destruction and invasion. In some tissues this process is effectively regulated by inhibitors of matrix-degrading, proteolytic enzymes. (c) Tumor cells migrate into the altered matrix, possibly moving as aggregates along guidance tracks provided by host structures (blood vessels, lymphatics, nerves) or matrix macromolecules (collagen and fibronectin tracks). Migration seems to be preceded by increased swelling of glycosaminoglycan (i.e., hyaluronate) in the matrix, ahead of the migrating cell population. Various host cell types (mast cells, fibroblasts, endothelial cells, macrophages, etc.) may participate in these events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Berenblum, I: Sequential aspects of chemical carcinogenesis: Skin. In: Becker, FF (ed) Cancer: a comprehensive treatise, vol 1, 2nd ed. Plenum Press, New York, 1982, pp 451–484.

    Google Scholar 

  2. Farber, E: Sequential events in chemical carcinogenesis. In: Becker, FF (ed) Cancer: a comprehensive treatise, vol 1, 2nd ed. Plenum Press, New York, 1982, pp 485–506.

    Google Scholar 

  3. Foulds, L: Neoplastic development, vol 1. Academic Press, New York, 1969.

    Google Scholar 

  4. Emmelot, P, Scherer, E: The first relevant cell stage in rat liver carcinogenesis. A quantitative approach. Biochim Biophys Acta 605: 247–304, 1980.

    Google Scholar 

  5. Farber, E, Cameron, R: The sequential analysis of cancer development. Adv. Cancer Res (31): 125–226, 1980.

    Google Scholar 

  6. McNutt, NS, Weinstein, RS: Carcinoma of the cervix: deficiency of nexus intercellular junctions. Science (165): 597–599, 1969.

    Google Scholar 

  7. Weinstein, RS, Zel, G, Merk, FB: Quantitation of occludens, adherens, and nexus cell junctions in human tumors. In: Schultz, J, Block, RE (eds) Membrane transformation in neoplasia. Academic Press, New York, 1974, pp 127–146.

    Google Scholar 

  8. Wallach, DFH: Membrane molecular biology of neoplastic cells. Elsevier Scientific Publ, New York, 1975.

    Google Scholar 

  9. Nicolson, GL: Trans-membrane control of the receptors on normal and tumor cells. II. Surface changes associated with transformation and malignancy. Biochim Biophys Acta (458): 1–27, 1976.

    Google Scholar 

  10. Poste, G, Weiss, L: Some considerations on cell surface alterations in malignancy. In: Weiss, L (ed). Fundamental aspects of metastasis. North-Holland Publ, Amsterdam, 1976, pp 25–47.

    Google Scholar 

  11. Weinstein, RS, Merk, FB, Alroy, J: The structure and function of intercellular junctions in cancer. Adv Cancer Res (23): 23–89, 1976.

    Google Scholar 

  12. Pauli, BU, Cohen, SM, Alroy, J, Weinstein, RS: Desmosome ultrastructure and the biological behavior of chemical carcinogen-induced urinary bladder carcinomas. Cancer Res (38): 3276–3285, 1978.

    Google Scholar 

  13. Graham, JM: Surface membrane enzymes in neoplasia. In: Hynes, RO (ed) Surfaces of normal and malignant cells. John Wiley & Sons, New York, 1979, pp 199–246.

    Google Scholar 

  14. Alroy, J, Pauli, BU, Weinstein, RS: Correlation between number of desmosomes and the aggressiveness of transitional cell carcinoma in human urinary bladder. Cancer (47): 104–112, 1981.

    Google Scholar 

  15. Fidler, IJ, Hart, IR: Biological diversity in metastatic neoplasms: origins and implications. Science (217): 998–1003, 1982.

    Google Scholar 

  16. Austin, CR: Recent progress in the study of eggs and spermatazoa: insemination and ovulation to implantation. In: Greep, PO (ed) Reproductive physiology, vol 8. University Park Press, Baltimore, 1974, pp 95–131.

    Google Scholar 

  17. Zaneveld, LJD: Capacitation of spermatazoa. In: Ludwig, H, Tauber, PF (eds) Human fertilization. Georg Thieme Verlag, Stuttgart, 1978, pp 128–136.

    Google Scholar 

  18. Schenk, RK, Wiener, J, Spiro, D: Fine structural aspects of vascular invasion of the tibial epiphyseal plate of growing rats. Acta Anat (69): 1–17, 1968.

    Google Scholar 

  19. Kuettner, KE, Pauli, BU: Vascularity of cartilage. In: Hall, BK (ed) Cartilage, vol 1. Academic Press, New York, 1982, pp 281–312.

    Google Scholar 

  20. Schoefl, GI: Studies on inflammation. III. Growing capillaries: their structure and permeability. Virchows Arch Pathol Anat (337): 97–141, 1963.

    Google Scholar 

  21. Gimbrone, MAJr, Martin, BM, Baldwin, WM, Unanue, ER, Cotran, RS: Stimulation of vascular cell growth by macrophage products. In: Nossel, HL, Vogel, HJ (eds) Pathobiology of the endothelial cell. Academic Press, New York, 1982, pp 3–17.

    Google Scholar 

  22. Cotran, RS: The endothelium and inflammation: new insights. In: Majno, G, Cotran, RS, Kaufman, N (eds) Current topics in inflammation and infection. Williams & Wilkens, Baltimore, 1982, pp 18–37.

    Google Scholar 

  23. Hashimoto, K, Yamanishi, Y and Dabbous, MK: Electron microscopic observations of collagenolytic activity of basal cell epithelioma of the skin in vivo and in vitro. Cancer Res (32): 2561–2567, 1972.

    Google Scholar 

  24. Liotta, LA, Tryggvason, K, Garbisa, S, Hart, I, Foltz, CM, Shafie, S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature (284): 67–68, 1980.

    Google Scholar 

  25. Woolley, DE, Tetlow, LC, Mooney, CJ, Evanson, JM: Human collagenase and its extracellular inhibitors in relation to tumor invasiveness. In: Sträuli, P, Barrett, AJ, Baici, A (eds) Proteinases and tumor invasion. Raven Press, New York, 1980, pp 97–115.

    Google Scholar 

  26. Kefalides, NA, Alper, R, Clark, CC: Biochemistry and metabolism of basement membranes. Int Rev Cytol (61): 167–228, 1979.

    Google Scholar 

  27. Bornstein, P, Sage, H: Structurally distinct collagen types. Ann Rev Biochem (49): 957–1003, 1980.

    Google Scholar 

  28. Franzblau, C, Faris, B: Elastin. In: Hay, ED (ed) Cell biology of extracellular matrix. Plenum Press, New York, 1981, pp 65–93.

    Google Scholar 

  29. Hascall, VC: Proteoglycans: structure and function. In: Ginsburg, V (ed) Biology of carbohydrates, Vol 1. John Wiley & Sons, New York, 1981, pp 1–49.

    Google Scholar 

  30. Hynes, RO: Fibronectin and its relation to cellular structure and behavior. In: Hay, ED (ed) Cell biology of extracellular matrix. Plenum Press, New York, 1981, pp 295–334.

    Google Scholar 

  31. Ruoslahti, E, Engvall, E, Hayman, E: Fibronectin: current concepts of its structure and function. Coll Res (1): 95–128, 1981.

    Google Scholar 

  32. Yamada, KM: Fibronectin and other structural proteins. In: Hay, ED (ed) Cell biology of extracellular matrix. Plenum Press, New York, 1981, pp 95–114.

    Google Scholar 

  33. Foster, JA. Elastin structure and biosynthesis: an overview. In: Cunningham, LW, Frederiksen, DW (eds) Methods in enzymology, vol 82. Academic Press, New York, 1982, pp 559–570.

    Google Scholar 

  34. Miller, EJ, Gay, S: Collagen: an overview. In: Cunningham, LW, Frederiksen, DW (eds) Methods in enzymology, vol 82. Academic Press, New York, 1982, pp 3–32.

    Google Scholar 

  35. Quigley, JP: Proteolytic enzymes of normal and malignant cells. In: Hynes, RO (ed) Surfaces of normal and malignant cells. John Wiley & Sons, New York, 1979, pp 247–285.

    Google Scholar 

  36. Gross, J, Highberger, JH, Johnson-Wint, B, Biswas, C: Mode of action and regulation of tissue collagenases. In: Woolley, DE, Evanson, JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, New York, 1980, pp 11–35.

    Google Scholar 

  37. Liotta, LA, Kleinerman, J, Catanzaro, P, Rynbrandt, D: Degradation of basement membrane by murine tumor cells. J Natl Cancer Inst (58): 1427–1431, 1977.

    Google Scholar 

  38. Harris, EDJr, Faulkner, CS, Wood, SJr: Collagenase in carcinoma cells. Biochem Biophys Res Commun (48): 1247–1253, 1972.

    Google Scholar 

  39. Bauer, EA, Gordon, JM, Reddick, ME, Eisen, AZ: Quantitation and immunocytochemical location of human skin collagenase in basal cell carcinoma. J Invest Dermatol (69): 363–367, 1977.

    Google Scholar 

  40. Biswas, C, Moran, WP, Bloch, KJ, Gross, J: Collagenolytic activity of rabbit V2 carcinoma growing at multiple sites. Biochem Biophys Res Commun (80): 33–38, 1978.

    Google Scholar 

  41. Werb, Z: Pathways for the modulation of macrophage collagenase activity. In: Horton, JE, Tarpley, TM, Davis, WF (eds) Mechanism of localized bone loss, special supplement to calcified tissue abstracts. Information Retrieval, Washington, DC 1978, pp 213–228.

    Google Scholar 

  42. Rifkin, DB, Gross, JL, Moscatelli, D, Gabrielides, C: The involvement of proteases and protease inhibitors in neovascularization. Acta Biol Med Ger (40): 1259–1263, 1981.

    Google Scholar 

  43. Sträuli, P, Weiss, L: Cell locomotion and tumor penetration. Eur J Cancer (13): 1–12, 1977.

    Google Scholar 

  44. Kraemer, PM: Mucopolysaccharides: cell biology and malignancy. In: Hynes, RO (ed) Surfaces of normal and malignant cells. John Wiley & Sons, New York, 1979, pp 149–198.

    Google Scholar 

  45. Toole, BP: Glycosaminoglycans in morphogenesis. In: Hay, ED (ed) Cell biology of extracellular matrix. Plenum Press, New York, 1981, pp 259–294.

    Google Scholar 

  46. Ruddon, RW: Cancer biology. Oxford University Press, Oxford, 1981, pp 120–210.

    Google Scholar 

  47. Weiss, J, Leibovich, SJ: A negative role for collagenase in observed differences between normal and rheumatoid polymeric collagen. In: Fricke, R, Hartmann, F (eds) Connective tissues: Biochemistry and pathophysiology. Springer-Verlag, New York, 1974, pp 278–280.

    Google Scholar 

  48. Woolley, DE, Glanville, RW, Roberts, DR, Evanson, JM: Purification, characterization and inhibition of human skin collagenase. Biochem J (169): 265–276, 1978.

    Google Scholar 

  49. Harris, EDJr, Vater, CA: Methodology of collagenase research: substrate preparation, enzyme action and purification. In: Woolley, DE, Evanson, JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, New York, 1980, pp 37–63.

    Google Scholar 

  50. Burleigh, MC: Degradation of collagen by non-specific proteinases. In: Barrett, AJ (ed) Proteinases in mammalian cells and tissues. North-Holland, Anmsterdam, 1977, pp 285–309.

    Google Scholar 

  51. Timpl, R, Rohde, H, Robey, P, Rennard, S, Foidart, J-M, Martin, G: Laminin-A glycoprotein from basement membranes. J Biol Chem (254): 9933–9937, 1979.

    Google Scholar 

  52. Stenman, S, Vaheri, A: Distribution of a major connective tissue protein, fibronectin, in normal human tissues. J Exp Med (147): 1054–1064, 1978.

    Google Scholar 

  53. Laurie, GW, Leblond, CP, Martin, GR: Localization of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin to the basal lamina of basement membranes. J Cell Biol (95): 340–344, 1982.

    Google Scholar 

  54. Kanwar, Y, Farquhar, MG: Presence of heparan sulfate in the glomerular basement membrane. Proc Natl Acad Sci USA (76): 1303–1307, 1979.

    Google Scholar 

  55. Miller, EJ, Gay, S, Haralson, MA, Martinez-Hernandez, A, Rhodes, RK: Chemistry and biology of the type V collagen system. In: Kuehn, K, Schoene, HH, Timpl, R (eds) New trends in basement membrane research. Raven Press, New York, 1982, pp 99–105.

    Google Scholar 

  56. Stone, PJ, Franzblau, C, Kagan, HM: Proteolysis of insoluble elastin. In: Cunningham, LW, Frederiksen, DW (eds) Methods in enzymology, vol 82. Academic Press, New York, 1982, pp 588–605.

    Google Scholar 

  57. Eaves, G: The invasive growth of malignant tumors as a purely mechanical process. J Pathol (109): 233–237, 1973.

    Google Scholar 

  58. Young, JS, Lumsden, CE, Stalker, AL: The significance of the ‘tissue pressure’ of normal testicular and neoplastic (Brown-Pearce carcinoma) tissue in the rabbit. J Pathol Bacteriol (62): 313–333, 1950.

    Google Scholar 

  59. Fidler, IJ, Gersten, DM, Hart, IR: The biology of cancer invasion and metastasis. Adv Cancer Res (28): 149–250, 1978.

    Google Scholar 

  60. Weinstein, RS: Origin and dissemination of human urinary bladder carcinoma. Sem Oncol (6): 149–156, 1979.

    Google Scholar 

  61. Harris, EDJr, Cartwright, EC: Mammalian collagenases. In: Barrett, AJ (ed) Proteinases in mammalian cells and tissues. North-Holland, Amsterdam, 1977, pp 249–283.

    Google Scholar 

  62. Harper, E: Collagenases. Ann Rev Biochem (49): 1063–1078, 1980.

    Google Scholar 

  63. Miller, EJ, Finch, JEJr, Chung, E, Butler, W: Specific cleavage of the native type III collagen molecule with trypsin. Similarity of the cleavage products to collagenase-produced fragments and primary structure at the cleavage site. Arch Biochem Biophys (173): 631–637, 1976.

    Google Scholar 

  64. Wang, H-M, Chan, J, Pettigrew, DW, Sodek, J: Cleavage of native type III collagen in the collagenase susceptible region by thermolysin. Biochim Biophys Acta (533): 270–277, 1978.

    Google Scholar 

  65. Gadek, J, Fells, G, Wright, D, Crystal, R: Human neutrophil elastase functions as a type III collagen ‘collagenase’. Biochem Biophys Res Commun (95): 1815–1822, 1980.

    Google Scholar 

  66. Mainardi, C, Hasty, D, Seyer, J, Kang, AH: Specific cleavage of human type III collagen by human polymorphoneuclear leukocyte elastase. J Biol Chem (255): 12006–12010, 1980.

    Google Scholar 

  67. Starkey, P, Barrett, AJ, Burleigh, MC: The degradation of articular collagen by neutrophil proteinases. Biochim Biophys Acta (483): 386–397, 1977.

    Google Scholar 

  68. Baici, A: Structure and breakdown of proteoglycans, collagen, and elastin. In: Sträuli, P, Barrett, AJ, Baici, A (eds) Proteinases and tumor invasion. Raven Press, New York, 1980, pp 17–47.

    Google Scholar 

  69. Koybayashi, S, Nagai, Y: Human leukocyte neutral proteases, with special reference to collagen metabolism. J Biochem (84): 559–567, 1978.

    Google Scholar 

  70. Liotta, LA, Abe, S, Gehron Robey, P, Martin, GR: Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proc Natl Acad Sci (76): 2268–2272, 1979.

    Google Scholar 

  71. Uitto, V-J, Schwartz, D, Veis, A: Degradation of basement-membrane collagen by neutral proteinases from human leukocytes. Eur J Biochem (105): 409–417, 1980.

    Google Scholar 

  72. Davies, M, Barrett, AJ, Travis, J, Sanders, E, Cole, GA: The degradation of human glomerular basement membrane with purified lysozomal proteinases: evidence for the pathogenic role of the polymorphonuclear leucocyte in glomerulonephritis. Clin Sci (54): 233–240, 1978.

    Google Scholar 

  73. Mainardi, CL, Dixit, SN, Kang, AH: Degradation of type IV (basement membrane) collagen by a proteinase isolated from human polymorphonuclear leukocyte granules. J Biol Chem (255): 5435–5441, 1980.

    Google Scholar 

  74. Liotta, LA, Goldfarb, RH, Brundage, R, Siegal, GP, Terranova, SV, Garbisa, S: Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res. (41): 4629–4636, 1981.

    Google Scholar 

  75. Liotta, LA, Tryggvasson, K, Garbisa, S, Gehron Robey, P, Abe, S: Partial purification and characterization of a neutral protease which cleaves type IV collagen. Biochem (20): 100–104, 1981.

    Google Scholar 

  76. Chung, E, Rhodes, RK, Miller, EJ: Isolation of three collagenous components of probable membrane origin from several tissues. Biochem Biophys Res Commun (71): 1167–1174, 1976.

    Google Scholar 

  77. Timpl, R, Bruckner, P, Fietzek, P: Characterization of pepsin fragments of basement membrane collagen obtained from a mouse tumor. Eur J Biochem (95): 255–263, 1979.

    Google Scholar 

  78. Schuppan, D, Timpl, R, Glanville, RW: Discontinuities in the triple helical sequence gly-x-y of basement membrane (type IV) collagen. FEBS Lett (115): 297–305, 1980.

    Google Scholar 

  79. Schwartz, DE, Chin-Quee, T, Veis, A: Characterization of bovine anterior-lens-capsule basement-membrane collagen. 1. Pepsin susceptibility, salt precipitation and thermal gelation: a property of non-collagen component integrity. Eur J Biochem (103): 21–27, 1980.

    Google Scholar 

  80. Schwartz, DE, Veis, A: Characterization of bovine anterior-lens-capsule basement-membrane collagen. 2. Segment long spacing precipitates: further evidence for large N-terminal and C-terminal extensions. Eur J Biochem (103): 29–37, 1980.

    Google Scholar 

  81. Timpl, R, Overbaumer, I, Furthmayr, H, Kuehn, K: Macromolecular organiaation of type IV collagen. In: Kuehn, K, Schoene, HH, Timpl, R, (eds) New trends in basement membrane research. Raven Press, New York, 1982, pp 57–67.

    Google Scholar 

  82. Schwartz, D, Arsenis, C, Kuettner, KE: Calcium dependence of human leukocyte elastase and its role in the degradation of intact basement membranes (abstract). Fed Proc (41): 1439, 1982.

    Google Scholar 

  83. Liotta, LA, Lanzer, WL, Garbisa, S: Identification of a type V collagenolytic enzyme. Biochem Biophys Res Commun (98): 184–190, 1981.

    Google Scholar 

  84. Mainardi, CL, Seyer, JM, Kang, AH: Type-specific collagenolysis: a type V collagen-degrading enzyme from macrophages. Biochem Biophys Res Commun (97): 1108–1115, 1980.

    Google Scholar 

  85. Malemud, C, Janoff, A: Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan. Arthritis Rheum (18): 361–368, 1975.

    Google Scholar 

  86. Keiser, H, Greenwald, R, Feinstein, G, Janoff, A: Degradation of cartilage proteoglycan by human leukocyte granule neutral proteinases-A model of joint injury. II. Degradation of isolated bovine nasal cartilage proteoglycan. J Clin Invest (57): 625–632, 1976.

    Google Scholar 

  87. Roughley, PJ, Barrett, AJ: The degradation of cartilage proteoglycans by tissue proteinases: proteoglycan structure and its susceptibility to proteolysis. Biochem J (167): 629–637, 1977.

    Google Scholar 

  88. Woolley, DE, Tetlow, LC, Evanson, JM: Collagenase immunolocalization studies of rheumatoid and malignant tissues. In: Woolley, DE, Evanson, JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, New York, 1980, pp 105–125.

    Google Scholar 

  89. Graf, M, Baici, A, Sträuli, P: Histochemical localization of Cathepsin B at the invasion front of the rabbit V2 carcinoma. Lab Invest (45): 587–596, 1981.

    Google Scholar 

  90. Carr, I, McGinty, F, Norris, P: The fine structure of neoplastic invasion: invasion of liver, skeletal muscle and lymphatic vessels by the Rd/3T3 tumour. J Pathol (118): 91–99, 1976.

    Google Scholar 

  91. Sträuli, P: A concept of tumor invasion. In: Sträuli, P, Barrett, AJ, Baici, A, (eds) Proteinases and tumor invasion. Raven Press, New York, 1980, pp 1–15.

    Google Scholar 

  92. Lunscken, C, Strauli, P: Penetration of an ascitic reticulum cell sarcoma of the golden hamster into the body wall and through the diaphragm. Virchows Arch B Cell Pathol (17): 247–259, 1975.

    Google Scholar 

  93. Dingemans, KP, Roos, E, van den, Bergh Weerman, MA, van de, Pavert, IV: Invasion of liver tissue by tumor cells and leukocytes: comparative ultrastructure. J Natl Cancer Inst (60): 583–598, 1978.

    Google Scholar 

  94. Riley, WBJr, Peacock, EEJr: Identification, distribution, and significance of a collagenolytic enzyme in human tissue. Proc Soc Exp Biol Med (124): 207–210, 1967.

    Google Scholar 

  95. Robertson, DM, Williams, DC: In vitro evidence of neutral collagenase activity in an invasive mammalian tumour. Nature (221): 259–260, 1969.

    Google Scholar 

  96. Taylor, AC, Levy, BM, Simpson, JW: Collagenolytic activity of sarcoma tissues in culture. Nature (228): 366–367, 1970.

    Google Scholar 

  97. Dresden, MH, Heilman, SA, Schmidt, JD: Collagenolytic enzymes in human neoplasms. Cancer Res (32): 993–996, 1972.

    Google Scholar 

  98. Yamanishi, Y, Dabbous, MK, Hashimoto, K: Effect of collagenolytic activity in basal cell epithelioma of the skin on reconstituted collagen and physical properties and kinetics of the crude enzyme. Cancer Res (32): 2551–2560, 1972.

    Google Scholar 

  99. Hashimoto, K, Yamanishi, Y, Maeyens, E, Dabbous, MK, Kanzaki, T: Collagenolytic activities of squamous cell carcinoma of the skin. Cancer Res. (33): 2790–2801, 1973.

    Google Scholar 

  100. Yamanishi, Y, Maeyens, E, Dabbous, MK, Ohyama, H, Hashimoto, K: Collagenolytic activity in malignant melanoma: physicochemical studies. Cancer Res (33): 2507–2512, 1973.

    Google Scholar 

  101. Abramson, M, Schilling, RW, Huang, C-C, Salome, RG: Collagenase activity in epidermoid carcinoma of the oral cavity and larynx. Ann Otol Rhinol Laryngol (84): 158–163, 1975.

    Google Scholar 

  102. McCroskery, PA, Richards, JF, Harris, EDJr: Purification and characterization of a collagenase extracted from rabbit tumours. Biochem J (152): 131–142, 1975.

    Google Scholar 

  103. Kuettner, KE, Soble, L, Croxen, RL, Marczynska, B, Hiti, J, Harper, E: Tumor cell collagenase and its inhibition by a cartilage-derived protease inhibitor. Science (196): 653–654, 1977.

    Google Scholar 

  104. Tane, N, Hashimoto, K, Kanzaki, T, Ohyama, H: Collagenolytic activities of cultured human malignant melanoma cells. J Biochem (84): 1171–1176, 1978.

    Google Scholar 

  105. Dabbous, MK, Roberts, AN, Brinkley, B: Collagenase and neutral protease activities in cultures of rabbit VX-2 carcinoma. Cancer Res (37): 3537–3544, 1977.

    Google Scholar 

  106. Dabbous, MK, Sobhy, C, Roberts, AN, Brinkley, B: Changes in the collagenolytic activity released by primary VX-2 carcinoma cultures as a function of tumor growth. Mol Cell Biochem (16): 37–42, 1977.

    Google Scholar 

  107. Ohyama, H, Hashimoto, K: Collagenase of human skin basal cell epithelioma. J Biochem, (82): 175–183, 1977.

    Google Scholar 

  108. Wirl, G: Extractable collagenase and carcinogenesis of the mouse skin. Connect Tissue Res (5): 171–178, 1977.

    Google Scholar 

  109. Wirl, G, Frick, J: Collagenase-A marker enzyme in human bladder cancer? Urol Res (7): 103–108, 1979.

    Google Scholar 

  110. Woolley, DE, Lindberg, KA, Glanville, RW Evanson, JM: Action of rheumatoid synovial collagenase on cartilage collagen. Different susceptibilities of cartilage and tendon collagen to collagenase attack. Eur J Biochem (50): 437–444, 1975.

    Google Scholar 

  111. Miller, EJ, Harris, EDJr, Chung, E, Finch, JEJr, McCroskery, PA, Butler, WT. Cleavage of type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. Biochem (15): 787–792, 1976.

    Google Scholar 

  112. Woolley, DE, Evanson, JM: Present status and future prospects in collagenase research. In: Woolley, DE, Evanson, JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, New York, 1980, pp 241–250.

    Google Scholar 

  113. Christman, JK, Silverstein, SC, Acs, G: Plasminogen activators. In: Barrett, AJ (ed) Research monographs in cell and tissue physiology, vol 2. North-Holland, Amsterdam, 1977, pp 91–149.

    Google Scholar 

  114. Neurath, H, Walsh, KA: Role of proteolytic enzymes in biological regulation (a review). Proc Natl Acad Sci (73): 3825–3832, 1976.

    Google Scholar 

  115. Ossowski, L, Quigley, JP, Kellerman, GM, Reich, E: 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): 1056–1064, 1973.

    Google Scholar 

  116. Unkelness, JC, Tobia, A, Ossowski, L, Quigley, JP, Rifkin, DB, Reich, E: An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. I. Chick embryo fibroblast cultures transformed by avian RNA tumor viruses. J Exp Med (137): 85–111, 1973.

    Google Scholar 

  117. Yunis, AA, Schultz, DR, Sato, GH: The secretion of fibrinolysin by cultured rat ovarian tumor cells. Biochem Biophys Res Commun (52): 1003–1012, 1973.

    Google Scholar 

  118. Pollack, R, Risser, R, Conlon, S, Rifkin, D: Plasminogen activator production accompanies loss of anchorage regulation in transformation of primary rat embryo cells by Simian virus 40. Proc Natl Acad Sci (71): 4792–4796, 1974.

    Google Scholar 

  119. Rifkin, DB, Loeb, JN, Moore, G, Reich, E: Properties of plasminogen activators formed by neoplastic human cell cultures. J Exp Med (139): 1317–1328, 1974.

    Google Scholar 

  120. Christman, JK, Silagi, S, Newcomb, EW, Silverstein, SC, Acs, G. Correlated suppression by 5-bromodeoxyuridine of tumorigenicity and plasminogen activator in mouse melanoma cells. Proc Natl Acad Sci (72): 47–50, 1975.

    Google Scholar 

  121. Laug, WE, Jones, PA, Benedict, WF: Relationship between fibrinolysis of cultured cells and malignancy. J Natl Cancer Inst (54): 173–179, 1975.

    Google Scholar 

  122. Howett, MK, High, CS, Rapp, F: Production of plasminogen activator by cells transformed by herpesviruses. Cancer Res (38): 1075–1078, 1978.

    Google Scholar 

  123. Chou, I-N, Black, PH, Roblin, RO: Suppression of fibrinolysin T activity fails to restore density-dependent growth inhibition to SV3T3 cells. Nature (250): 739–741, 1974.

    Google Scholar 

  124. Mott, DM, Fabisch, PH, Sani, BP, Sorof, S: Lack of correlation between fibrinolysis and the transformed state of cultured mammalian cells. Biochem Biophys Res Commun (61): 621–627, 1974.

    Google Scholar 

  125. Wolf, BA, Goldberg, AR: Rous-sarcoma-virus-trans-formed fibroblasts having low levels of plasmibogen activator. Proc Natl Acad Sci (73): 3613–3617, 1976.

    Google Scholar 

  126. Montesano, R, Drevon, C, Kuroki, T, Saint Vincent, L, Handleman, S, Sanford, KK, Defeo, D, Weinstein, IB: Test for malignant transformation of rat liver cells in culture: cytology, growth in soft agar, and production of plasminogen activator. J Natl Cancer Inst (59): 1651–1658, 1977.

    Google Scholar 

  127. Freedman, VH, Shin, S-I: Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell (3): 355–359, 1974.

    Google Scholar 

  128. Goldfarb, RH, Quigley, JP: Synergistic effect of tumor virus transformation and tumor promotor treatment on the production of plasminogen activator by chick embryo fibroblasts. Cancer Res (38): 4601–4609, 1978.

    Google Scholar 

  129. Arstedt, B, Holmberg, L: Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature (261): 595–596, 1976.

    Google Scholar 

  130. Vetterlein, D, Young, PL, Bell, TE, Roblin, R: Immunological characterization of multiple molecular weight forms of human cell plasminogen activators. J Biol Chem (254): 575–578, 1979.

    Google Scholar 

  131. Paranjpe, M, Engel, L, Young, N, Liotta, LA: Activation of human breast carcinoma through plasminogen activator. Life Sci (26): 1223–1231, 1980.

    Google Scholar 

  132. Mikuni-Takagaki, Y, Gross, J: Degradation of cartilage matrix by Yoshida sarcoma cells. In: Yamakawa, T, Osawa, T, Handa, S (eds) Glycoconjugates. Japan Scientific Societies Press, Tokyo, 1981, pp 491–492.

    Google Scholar 

  133. Machianami, R: A study on the invasive growth of malignant tumors. I. An electron microscopic study of the invasive growth of Yoshida sarcoma cells into the rat articular cartilage. Acta Pathol Jpn (22): 19–39, 1972.

    Google Scholar 

  134. Hornebeck, W, Derouette, JC, Brechemier, D, Adnet, JJ, Robert, L: Elastogenesis and elastinolytic activity in human breast cancer. Biomedicine (26): 48–52, 1977.

    Google Scholar 

  135. Hornebeck, W, Brechemier, D, Bellon, G, Adnet, JJ, Robert, L: Biological significance of elastase-like enzymes in arteriosclerosis and human breast cancer. In: Strauli, P, Barrett, AJ, Baici, A (eds) Proteinases and tumor invasion. Raven Press, New York, 1980, pp 117–141.

    Google Scholar 

  136. Kao, RT, Wong, M, Stern, R: Elastin degradation by proteases from cultured human breast cancer cells. Biochem Biophys Res Commun (105): 383–389, 1982.

    Google Scholar 

  137. Folkman, J, Cotran, R: Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol (16): 207–248, 1976.

    Google Scholar 

  138. Moscatelli, D, Jaffe, EA, Rifkin, DB: Phorbol esters stimulate protease production in human endothelial cells. In: Hecker, E, Fusenig, NE, Kunz, W, Marks, F, Thielmann, HW (eds) Carcinogenesis-A comprehensive survey, vol 7. Raven Press, New York, 1982, pp 401–404.

    Google Scholar 

  139. Kuettner, KE, Hiti, J, Eisenstein, R, Harper, E: Collagenase inhibition by cationic proteins derived from cartilage and aorta. Biochem Biophys Res Commun (72): 40–46, 1976.

    Google Scholar 

  140. Azizkhan, RG, Azizkhan, JC, Zetter, BR, Folkman, J: Mast cell heparin stimulates migration of capillary endothelial cells in vitro. J Exp Med (152): 931–944, 1980.

    Google Scholar 

  141. Coman, DR: Decreased mutual adhesiveness, a property of cells from squamous cell carcinomas. Cancer Res (4): 625–629, 1944.

    Google Scholar 

  142. Coman, DR: Adhesiveness and stickiness: two independent properties of the cell surface. Cancer Res (21): 1436–1438, 1961.

    Google Scholar 

  143. Steinberg, MS: Reconstruction of tissues by dissociated cells. Science (141): 401–408, 1963.

    Google Scholar 

  144. Coman, DR, Anderson, TF: A structural difference between the surfaces of normal and carcinomatous epidermal cells. Cancer Res (15): 541–543, 1955.

    Google Scholar 

  145. Berwick, L, Coman, DR: Some chemical factors in cellular adhesion and stickiness. Cancer Res (22): 982–986, 1962.

    Google Scholar 

  146. Coman, DR: Reduction in cellular adhesiveness upon contact with a carcinogen. Cancer Res (20): 1202–1204, 1960.

    Google Scholar 

  147. Muir, AR: The effects of divalent cations on the ultrastructure of the perfused rat heart. J Anat (101): 239–261, 1967.

    Google Scholar 

  148. Barr, L, Berger, W, Dewey, MM: Electrical transmission of the nexus between smooth muscle cells. J Gen Physiol (51): 347–368, 1968.

    Google Scholar 

  149. Goodenough, DA, Gilula, NB: The splitting of hepatocyte gap junctions and zonulae occludentes with hypertonic disaccharides. J Cell Biol (61): 575–590, 1974.

    Google Scholar 

  150. Alroy, J, Banner, BF, Pauli, BU, Leav, I: Alterations of intercellular junctions in acinic cell carcinoma of the canine pancreas. Virchows Arch B Cell Pathol (28): 21–30, 1978.

    Google Scholar 

  151. McNutt, NS, Hershberg, RA, Weinstein, RS: Further observations on the occurence of nexuses in benign and malignant human cervical epithelium. J Cell Biol (51): 805–825, 1971.

    Google Scholar 

  152. Pauli, BU, Weinstein, RS, Alroy, J, Arai, M: Ultrastructure of cell junctions in FANFT-induced urothelial tumors in urinary bladder of Fischer rats. Lab Invest (37): 609–621, 1977.

    Google Scholar 

  153. Weinstein, RS, Pauli, BU: Cell relationships in epithelia. In: Koss, LG, Coleman, DV (eds) Advances in clinical cytology. Butterworth, London, 1981, pp 160–200.

    Google Scholar 

  154. Pauli, BU, Kuettner, KE, Weinstein, RS: Intercellular junctions in FANFT-induced carcinomas of rat urinary bladder in tissue culture: in situ thin-section, freeze-fracture, and scanning electron microscopy studies. J Microsc (115): 271–282, 1979.

    Google Scholar 

  155. Sylven, B: Biochemical and enzymatic factors involved in cellular detachment. In: Garattini, S, Franchi, G (eds) Chemotherapy of cancer dissemination and metastasis. Raven Press, New York, 1973, pp 129–138.

    Google Scholar 

  156. Sylven, B: Biochemical factors involved in the cellular detachment from tumors. Schweiz Med Wochenschr (104): 258–261, 1974.

    Google Scholar 

  157. Hatcher, VB, Wertheim, MS, Rhee, CY, Tsien, G, Burk, PG: Relationship between cell surface protease activity and doubling time in various normal and transformed cells. Biochim Biophys Acta (451): 499–510, 1976.

    Google Scholar 

  158. Pauli, BU, Weinstein, RS: Correlations between cell surface protease activities and abnormalities of occludens junctions in rat bladder carcinoma in vitro. Cancer Res. (42): 2289–2297, 1982.

    Google Scholar 

  159. Weiss, L: The cell periphery, metastasis and other contact phenomena. North-Holland, Amsterdam, 1967.

    Google Scholar 

  160. Weiss, L, Holyoke, ED: Some effects of hypervitaminosis A on metastasis of spontaneous breast cancer in mice. J Natl Cancer Inst (43): 1045–1053, 1969.

    Google Scholar 

  161. Ambrose, EJ, Easty, DM: Time lapse filming of cellular interactions in organ culture. I. Behavior of non-malignant cells. Differentiation (1): 39–50, 1973.

    Google Scholar 

  162. Ambrose, EJ, Easty, DM: Time lapse filming of cellular interactions in organ culture. II. Behavior of malignant cells. Differentiation (1): 277–284, 1973.

    Google Scholar 

  163. Wood, SJr: Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. Arch Pathol (66): 550–568, 1958.

    Google Scholar 

  164. Wood, SJr, Baker, RR, Marzocchi, B: In vivo studies of tumor behavior: locomotion of and interrelationships between normal cells and cancer cells. In: The proliferation and spread of neoplastic cells. Williams & Wilkins, Baltimore, 1968, pp 495–509.

    Google Scholar 

  165. Vesely, P, Weiss, RA: Cell locomotion and contact inhibition of normal and neoplastic rat cells. Int J Cancer (11): 64–76, 1973.

    Google Scholar 

  166. Harris, A: Contact inhibition of cell locomotion. In: Cox, RP (ed) Cell communication. John Wiley & Sons, New York, 1974, pp 147–185.

    Google Scholar 

  167. Abercrombie, M, Heaysman, JEM: Observations on the social behavior of cells in tissue culture. I. Speed of movement of chick heart fibroblasts in relation to their mutual contacts. Exp Cell Res (5): 111–131, 1953.

    Google Scholar 

  168. Abererombie, M, Heaysman, JEM. Observations on the social behavior of cells in tissue culture. II. ‘Monolayering’ of fibroblasts. Exp Cell Res (6): 293–306, 1954.

    Google Scholar 

  169. Abercrombie, M, Ambrose, EJ: Interference microscope studies of cell contacts in tissue culture. Exp Cell Res (15): 332–345, 1958.

    Google Scholar 

  170. Abercrombie, M: Contact inhibition in tissue culture. In Vitro (6): 128–142, 1970.

    Google Scholar 

  171. Stephenson, EM, Stephenson, NG: Invasive locomotory behavior between malignant human melanoma cells and normal fibroblasts filmed in vitro. J Cell Sci (32): 389–418, 1978.

    Google Scholar 

  172. Abercrombie, M, Heaysman, JEM, Karthauser, HM: Social behaviour of cells in tissue culture. III. Mutual influence of sarcoma cells and fibroblasts. Exp Cell Res (13): 276–291, 1957.

    Google Scholar 

  173. Abercrombie, M, Heaysman, JEM: Invasive behavior between sarcoma and fibroblast populations in cell culture. J Natl Cancer Inst (56): 561–570, 1976.

    Google Scholar 

  174. Abercrombie, M, Ambrose, EJ: The surface properties of cancer cells: a review. Cancer Res (22): 525–548, 1962.

    Google Scholar 

  175. Martz, E, Steinberg, MS: The role of cell-cell contact in ‘contact’ inhibition of cell division: a review and new evidence. J Cell Physiol (79): 189–210, 1972.

    Google Scholar 

  176. Steinberg, MS: Cell movement in confluent monolayers: a re-evaluation of the causes of ‘contact inhibition’. In: Abercrombie, M (ed) Locomotion of tissue cells (Ciba Foundation Symposium). Associated Scientific Publishers, Amsterdam, 1973, pp 333–355.

    Google Scholar 

  177. Wiseman, LL, Steinberg, MS: The movement of single cells within solid tissue masses. Exp Cell Res (79): 468–471, 1973.

    Google Scholar 

  178. Easty, GC, Easty, DM: An organ system for the examination of tumour invasion. Nature (199): 1104–1105, 1963.

    Google Scholar 

  179. Lattner, AL, Longstaff, E, Lunn, JM: Invasive properties of histone transformed cells. Br J Cancer (25): 568–573, 1971.

    Google Scholar 

  180. Easty, DM, Easty, GC: Measurement of the ability of cells to infiltrate normal tissues in vitro. Br J Cancer (29): 36–49, 1974.

    Google Scholar 

  181. Schleich, AB, Frick, M, Mayer, A: Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants. J Natl Cancer Inst (56): 221–237, 1976.

    Google Scholar 

  182. de, Rinder, L, Mareel, M, Vakaet, L: Invasion of malignant cells into cultured embryonic substrates. Arch Geschwulstforsch (47): 7–27, 1977.

    Google Scholar 

  183. Hart, I, Fidler, IJ: An in vitro quantitative assay for tumor cell invasion. Cancer Res (38): 3218–3224, 1978.

    Google Scholar 

  184. Mareel, M, Kint, J, Meyvisch, C: Methods of study of the invasion of malignant C3H-mouse fibroblasts into embryonic chick heart in vitro. Virchows Arch B Cell Pathol (30): 95–111, 1979.

    Google Scholar 

  185. Lohmann-Matthes, M-L, Schleich, A, Shantz, G, Schirrmacher, V: Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. VII. Interaction of metastasizing and non-metastasizing tumors with normal tissues in vitro. J Natl Cancer Inst (64): 1413–1425, 1980.

    Google Scholar 

  186. Mareel, MM: Recent aspects of tumor invasiveness. Int Rev Exp Pathol (22): 65–129, 1980.

    Google Scholar 

  187. Mareei, M, Bruyneel, E, Storme, G: Attachment of mouse fibrosarcoma cells to precultured fragments of embryonic chick heart. An early step of invasion in vitro. Virchows Arch B Cell Pathol (34): 85–97, 1980.

    Google Scholar 

  188. Pauli, BU, Anderson, SN, Memoli, VA, Kuettner, KE: Development of an in vitro and in vivo epithelial tumor model for the study of invasion. Cancer Res (40): 4571–4580, 1980.

    Google Scholar 

  189. Poste, G, Doll, J, Hart, IR, Fidler, IJ: In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties. Cancer Res (40): 1636–1644, 1980.

    Google Scholar 

  190. Pauli, BU, Memoli, VA, Kuettner, KE: In vitro determination of tumor invasiveness using extracted hyaline cartilage. Cancer Res (41): 2084–2091, 1981.

    Google Scholar 

  191. De, Haan, RL: Migration patterns of the precardiac mesoderm in the early chick embryo. Exp Cell Res (29): 544–560, 1963.

    Google Scholar 

  192. Vaughan, RB, Trinkaus, JP: Movements of epithelial cell sheets in vitro. J Cell Sci (1): 407–413, 1966.

    Google Scholar 

  193. Kolega, J: The movement of cell clusters in vitro: morphology and directionality. J Cell Sci (49): 15–32, 1981.

    Google Scholar 

  194. Enterline, HT, Coman, DR: The ameboid motility of human and animal neoplastic cells. Cancer (3): 1033–1038, 1950.

    Google Scholar 

  195. Culp, LA, Murray, BA, Rollins, BJ: Fibronectin and proteoglycans as determinants of cell-substratum adhesion. J Supramol Struct Cell Biochem (11): 401–427, 1979.

    Google Scholar 

  196. Rollins, BJ, Culp, LA: Glycosaminoglycans in the substrate adhesion sites of normal and virus-transformed murine cells. Biochem (18): 141–148, 1979.

    Google Scholar 

  197. Atherly, AG, Barnhart, BJ, Kraemer, PM: Growth and biochemical characteristics of a detachment variant of CHO cells. J Cell Physiol (90): 375–386, 1977.

    Google Scholar 

  198. Barnhart, BJ, Cox, SH, Kraemer, PM: Detachment variants of Chinese hamster cells. Hyaluronic acid as a modulator of cell detachment. Exp Cell Res (119): 327–332, 1979.

    Google Scholar 

  199. Fisher, M, Solursh, M: The influence of the substratum on mesenchyme spreading in vitro. Exp Cell Res (123): 1–14, 1979.

    Google Scholar 

  200. Toole, BP, Trelstad, RL: Hyaluronate production and removal during corneal development in the chick. Dev Biol (26): 28–35, 1971.

    Google Scholar 

  201. Toole, BP, Gross, J: The extracellular matrix of the regenerating newt limb: synthesis and removal of hyaluronate prior to differentiation. Dev Biol (25): 57–77, 1971.

    Google Scholar 

  202. Iwata, H, Urist, MR: Hyaluronic acid production and removal during bone morphogenesis in implants of bone matrix in rats. Clin Orthop (90): 236–245, 1973.

    Google Scholar 

  203. Reid, T, Flint, MH: Changes in glycosaminoglycan content of healing rabbit tendon. J Embryol Exp Morphol (31): 489–495, 1974.

    Google Scholar 

  204. Toole, BP, Biswas, C, Gross, J: Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci (76): 6299–6303, 1979.

    Google Scholar 

  205. Fisher, B, Fisher, ER, Feduska, N: Trauma and the localization of tumor cells. Cancer (20): 23–30, 1967.

    Google Scholar 

  206. Hayashi, H, Yoshida, K, Ozaki, T, Ushijima, K: Chemotactic factor associated with invasion of cancer cells. Nature (226): 174–175, 1970.

    Google Scholar 

  207. Pauli BU, Kuettner KE: Host tissue resistance to tumor invasion. In: Mareel M, Calman K (eds) Invasion. Oxford University Press, Oxford (in press).

  208. Romualdez, AGJr, Ward, PA: A unique complement derived chemotactic factor for tumor cells. Proc Natl Acad Sci (72): 4128–4132, 1975.

    Google Scholar 

  209. Orr, W, Varani, J, Ward, PA: Characteristics of the chemotactic response of neoplastic cells to a factor derived from the fifth component of complement. Am J Pathol (93): 405–422, 1978.

    Google Scholar 

  210. Orr, W, Phan, SH, Varani, J, Ward, PA, Kreutzer, DL, Webster, RO, Henson, PM: Chemotactic factor for tumor cells derived from C5a fragment of complement component C5. Proc Natl Acad Sci (76): 1986–1989, 1979.

    Google Scholar 

  211. Orr, W, Varani, J, Gondek, MD, Ward, PA, Mundy, GR: Chemotactic responses of tumor cells to products of resorbing bone. Science (203): 176–179, 1979.

    Google Scholar 

  212. Orr, FW, Varani, J, Kreutzer, DL, Senior, RM, Ward, PA: Digestion of the fifth component of complement by leukocyte enzymes. Sequential generation of chemotactic activities for leukocytes and for tumor cells. Am J Pathol (94): 75–84, 1979.

    Google Scholar 

  213. Lam, WC, Delikatny, EJ, Orr, FW, Wass, J, Varani, J, Ward, PA: The chemotactic response of tumor cells. A model for cancer metastasis. Am J Pathol (104): 69–76, 1981.

    Google Scholar 

  214. Ushijima, K, Nishi, H, Ishikura, A, Hayashi, H: Characterization of two different factors chemotactic for cancer cells from tumor tissue. Virchows Arch B Cell Pathol (21): 119–131, 1976.

    Google Scholar 

  215. Kuettner, KE, Pauli, BU, Soble, L: Morphological studies on the resistance of cartilage to invasion by osteosarcoma cells in vitro and in vivo. Cancer Res (38): 277–287, 1978.

    Google Scholar 

  216. Kuettner, KE, Pauli, BU: Resistance of cartilage to normal and neoplastic invasion. In: Horton, JE, Tarpley, TM, Davis, WF (eds) Mechanism of localized bone loss, special supplement to calcified tissue abstracts. Information Retrieval, Washington DC, 1978, pp 251–278.

    Google Scholar 

  217. Kuettner, KE, Pauli, BU: Resistance of cartilage to invasion. In: Weiss, L, Gilbert, HA (eds) Bone metastasis. GK Hall, Boston, 1981, pp 131–165.

    Google Scholar 

  218. Pauli, BU, Kuettner, KE, The regulation of invasion by a cartilage-derived anti-invasion factor. In: Liotta, LA, Hart, IR (eds) Tumor invasion and metastasis. Martinus Nijhoff Publ, Boston, 1982, pp 267–290.

    Google Scholar 

  219. Sorgente, N, Kuettner, KE, Eisenstein, R: The isolation, purification, and partial characterization of proteinase inhibitors from bovine cartilage and aorta. In: Peeters, H (ed) Proceedings of the 23rd Colloquium on Protides of the Biological Fluids. Pergamon Press, Oxford, 1976, pp 227–230.

    Google Scholar 

  220. Roughley, PJ, Murphy, G, Barrett, AJ: Proteinase inhibitors of bovine nasal cartilage. Biochem J (169): 721–724, 1978.

    Google Scholar 

  221. Rifkin, DB, Crowe, RM: Isolation of a protease inhibitor from tissues resistant to tumor invasion. Hoppe Seylers Z Physiol Chem (358): 1525–1531, 1977.

    Google Scholar 

  222. Kuettner, KE, Arsenis, C, Schwartz, D, Thonar, EJM, Pauli, BU: Resistance of cartilage to invasive processes (abstract). In: Symposium on Connective Tissue in Health and Disease. Monash University, Melbourne, 1982, p 17.

    Google Scholar 

  223. Pauli, BU, Memoli, VA, Kuettner, KE: Regulation of tumor invasion by cartilage-derived anti-invasion factor in vitro. J Natl Cancer Inst (67): 65–73, 1981.

    Google Scholar 

  224. Sorgente, N, Dorey, CK: Inhibition of endothelial cell growth by a factor isolated from cartilage. Exp Cell Res (128): 63–71, 1980.

    Google Scholar 

  225. Brem, H, Folkman, J: Inhibition of tumor angiogenesis mediated by cartilage. J Exp Med (141): 427–439, 1975.

    Google Scholar 

  226. Eisenstein, R, Schumacher, BS, Meineke, C, Matijevitch, B, Kuettner, KE: Growth regulators in connective tissue. Systemic administration of an aortic extract inhibits tumor growth in mice. Am J Pathol (91): 1–10, 1978.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pauli, B.U., Schwartz, D.E., Thonar, E.JM. et al. Tumor invasion and host extracellular matrix. Cancer Metast Rev 2, 129–152 (1983). https://doi.org/10.1007/BF00048966

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00048966

Keywords

Navigation