Proteolytic Enzymes in Tumor Invasion and Degradation of Host Extracellular Matrices

  • Chapter
Mechanisms of Cancer Metastasis

Part of the book series: Developments in Oncology ((DION,volume 40))

Abstract

A fact widely recognized by clinical oncologists is that rather than the primary tumor, the secondary metastatic tumor(s) usually leads to the lethality of human malignant disease (1–4). Tumor invasion, the destructive penetration of surrounding normal tissues by malignant cells, is an important feature of the metastatic spread and dissemination of cancer (5–9). Invasive tumor cells must penetrate a number of host extracellular barriers and matrices, including basement membranes, at several stages of tumor metastasis. Investigation of the biochemical mechanisms involved in tumor invasion and degradation of host extracellular matrices have indicated that proteolytic enzymes play a role in these processes (5–13). This chapter will review the role of various proteolytic enzymes in the destruction of several host matrices and their specific components during tumor invasion and metastasis. In addition, the potential significance of matrix degradation by proteolytic enzymes during tumor invasion to the diagnosis and therapy of human metastatic disease will be discussed.

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

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Sugarbaker EV, Weingard DN, Roseman JM: Observations on cancer metastasis in man. IN: Liotta LA and Hart IR (eds.) Tumor Invasion and Metastasis. Martinus Nijhoff, The Hague, pp. 427–465, 1982.

    Google Scholar 

  3. Poste G, Fidler IJ: The pathogenesis of cancer metastasis. Nature (London) 283: 139–146, 1980.

    Article  CAS  Google Scholar 

  4. Hart IR, Fidler IJ: Cancer invasion and metastasis. Quart. Rev. Biol. 55: 121–142, 1980.

    Article  PubMed  CAS  Google Scholar 

  5. Jones PA, DeClerck YA: Extracellular matrix destruction by invasive tumor cells. Cancer Metastasis Rev. 1: 289–317, 1982.

    Article  PubMed  CAS  Google Scholar 

  6. Pauli BU, Schwartz DE, Thonar EJ-M, Keuttner K: Tumor invasion and host extracellular matrix. Cancer Metastasis Rev. 2: 129–152, 1983.

    Article  PubMed  CAS  Google Scholar 

  7. Liotta LA, Rao CN, Barsky SH: Tumor invasion and the extra- cellular matrix. Lab. Invest. 49: 636–649, 1983.

    PubMed  CAS  Google Scholar 

  8. Liotta LA, Goldfarb RH: Interactions of tumor cells with the basement membrane of endothelium. IN: Honn KV and Sloane BF (eds.) Hemostatic Mechanisms and Metastasis. Martinus Nijhoff, The Hague, pp. 319–336, 1984.

    Chapter  Google Scholar 

  9. Liotta LA, Garbisa S, Tryggvason K: Biochemical mechanisms involved in tumor cell penetration of the basement membrane. IN: Liotta LA and Hart IR (eds.) Tumor Invasion and Metastasis. Martinus Nijhoff, The Hague, pp. 318–333, 1982.

    Google Scholar 

  10. Strauli P, Barrett AJ, Baici A (eds.):Proteinases and Tumor Invasion. Raven Press, New York, 1980.

    Google Scholar 

  11. Liotta LA, Thorgeirsson UP, Garbisa S: Role of collagenases in tumor cell invasion. Cancer Metastasis Rev. 1: 277–288, 1982.

    Article  PubMed  CAS  Google Scholar 

  12. Recklies AD, Poole AR: Proteolytic mechanisms of tissue destruction in tumor growth and metastasis. IN: Weiss L and Gilbert HA (eds.) Liver Metastasis. GK Hall, Boston, pp. 77–95, 1982.

    Google Scholar 

  13. Goldfarb RH: Proteases in tumor invasion and metastasis. IN: Liotta and Hart IR (eds.) Tumor Invasion and Metastasis. Martinus Nijhoff, The Hague, pp. 375–390, 1982.

    Google Scholar 

  14. Barsky SH, Siegal GP, Jannotta F, Liotta LA: Loss of basement membrane components by invasive tumors but not by their benign counterparts. Lab. Invest. 49: 140–147, 1983.

    PubMed  CAS  Google Scholar 

  15. Barsky SH, Rao CN, Grotendorst GR, Liotta LA: Increased content of type V collagen in desmoplasia of human breast carcinoma. Am. J. Pathol. 108: 276–282, 1982.

    PubMed  CAS  Google Scholar 

  16. Alitalo K, Vaheri A: Pericellular matrix in malignant transformation. Adv. Cancer Res. 37: 111–158, 1982.

    Article  PubMed  CAS  Google Scholar 

  17. Auersperg N, Erber H, Worth A: Histologic variation among poorly differentiated invasive carcinomas of the human uterine cervix. J. Natl. Cancer Inst. 51: 1461–1477, 1973.

    PubMed  CAS  Google Scholar 

  18. Bissell MJ, Hall HG, Parry G: How does the extracellular matrix direct gene expression ? J. Theor. Biol. 99: 31–64, 1982.

    Article  PubMed  CAS  Google Scholar 

  19. Nicolson GL: Cancer metastasis organ colonization and the cell-surface properties of malignant cells. Biochim. Biophys. Acta 695: 113–176, 1982.

    PubMed  CAS  Google Scholar 

  20. Nicolson GL, Poste G: Tumor cell diversity and host responses in cancer metastasis–part 1, properties of metastatic cells. Curr. Prob. Cancer 7: 1–83, 1982.

    Article  CAS  Google Scholar 

  21. Nicolson GL: Tumor implantation and invasion at metastatic sites. Int. Rev. Exp. Pathol. 25: 77–181, 1983.

    PubMed  CAS  Google Scholar 

  22. Yamada KM: Cell surface interactions with extracellular materials. Ann. Rev. Biochem. 52: 761–799, 1983.

    Article  PubMed  CAS  Google Scholar 

  23. Murray JC, Liotta LA, Rennard SI, Martin GR: Adhesion characteristics of murine metastatic and nonmetastatic tumor cells in vitro. Cancer Res. 40: 347–351, 1980.

    PubMed  CAS  Google Scholar 

  24. Terranova VP, Liotta LA, Russo RG, Martin GR: Role of laminin in the attachment and metastasis of murine tumor cells. Cancer Res. 42: 2265–2269, 1982.

    PubMed  CAS  Google Scholar 

  25. Terranova VP, Rao CN, Kalebic T, Margulies IM, Liotta LA: Laminin receptor on human breast carcinoma cells. Proc. Natl. Acad. Sci. USA 80: 444–448, 1983.

    Article  PubMed  CAS  Google Scholar 

  26. Liotta LA, Goldfarb RH, Terranova VP: Cleavage of laminin by thrombin and plasmin: Alpha thrombin selectively cleaves the beta chain of laminin. Thromb. Res. 21: 663–673, 1981.

    Article  PubMed  CAS  Google Scholar 

  27. Rao CN, Margulies INK, Tralka TS, Terranova VP, Madri JA, Liotta LA: Isolation of a subunit of laminin and its role in molecular structure and tumor cell attachment. J. Biol. Chem. 257: 9740–9744, 1982.

    PubMed  CAS  Google Scholar 

  28. Rao CN, Margulies IMK, Goldfarb RH, Madri JA, Woodley DT, Liotta LA: Differential proteolytic susceptibility of laminin alpha and beta subunits. Arch. Biochem. Biophys. 219: 65–70, 1982.

    Article  PubMed  CAS  Google Scholar 

  29. Weiss L, Ward PM: Cell detachment and metastasis. Cancer Metastasis Rev. 2: 111–127, 1983.

    Article  PubMed  CAS  Google Scholar 

  30. Lacovara J, Cramer EB, Quigley JP: Fibronectin enhancement of directed migration of B16 melanoma cells. Cancer Res. 44: 1657–1663, 1984.

    PubMed  CAS  Google Scholar 

  31. McCarthy JB, Furcht LT: Laminin and fibronectin promote the haptotactic migration of B16 melanoma cells in vitro. J. Cell Biol. 98: 1474–1480, 1984.

    Article  PubMed  CAS  Google Scholar 

  32. Thorgeirsson UP, Liotta LA, Kalebic T, Margulies IM, Thomas K, Rios-Candelore M, Russo KG: Effect of natural protease inhibitors and a chemoattractant on tumor cell invasion in vitro. J. Natl. Cancer Inst. 69: 1049–1054, 1982.

    PubMed  CAS  Google Scholar 

  33. Russo RG, Thorgeirsson U, Liotta LA: In vitroquantitative assay of invasion using human amnion. IN: Liotta LA and Hart IR (eds.) Tumor Invasion and Metastasis. Martinus Nijhoff, The Hague, pp. 173–187, 1982.

    Google Scholar 

  34. Quigley JP: Proteolytic enzymes of normal and malignant cells. IN: Hynes RO (ed.) Surfaces of Normal and Malignant Cells. John Wiley and Sons, Chichester, pp. 247–285, 1979.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  36. Starkey JR, Hosick H, Stanford DR, Liggitt HD: Interaction of metastatic tumor cells with bovine lens capsule basement membrane. Cancer Res. 44: 1585–1594, 1984.

    PubMed  CAS  Google Scholar 

  37. Nakajima M, Custead SE, Welch DR, Nicolson GL: Type IV collagenase: Relation to metastatic properties of rat 13762 mammary adenocarcinoma metastatic clones. Proc. Am. Assoc. Cancer Res. 24: 62, 1984.

    Google Scholar 

  38. Shields SE, Ogilvie DJ, McKinnell RG, Tarin D: Degradation of basement membrane collagens by metalloproteases released by human, murine, and amphibian tumors. J. Pathol. 143: 193–197, 1984.

    Article  PubMed  CAS  Google Scholar 

  39. Turpeenniemi-Hujanen T, Thorgeirsson UP, Hart I, Liotta LA: Expression of basement membrane collagen degrading metalloprotease activity in tumor cell hybrids which differ in metastatic potential. Proc. Am. Assoc. Cancer Res. 24: 62, 1984.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  41. Mainardi LL, Seyer JM, Kang AH: Specific collagenolysis: Identification of a type V degrading activity in alveolar macrophages. Biochem. Biophys. Res. Commun. 97: 1108–1115, 1980.

    Article  PubMed  CAS  Google Scholar 

  42. Mainardi C, Dixit SN, Kang AH: Degradation of type IV (basement membrane) collagen by a proteinase isolated from polymorphonuclear leukocyte granules. J. Biol. Chem. 225: 5435–5441, 1980.

    Google Scholar 

  43. Liotta LA, Wicha MS, Foidart JM, Rennard SI, Garbisa S, Kidwell WR: Hormonal requirements for basement membrane collagen deposition by cultured rat mammary epithelium. Lab. Invest. 41: 511–518, 1979.

    PubMed  CAS  Google Scholar 

  44. Henry N,Eeckhout Y, van Lamsweerde A-L, Vaes G: Cooperation between metastatic tumor cells and macrophages in the degradation of basement membrane (type IV) collagen. FEBS Lett. 161:243–246, 1983.

    Google Scholar 

  45. Reich E: Activation of plasminogen: A general mechanism for producing localized extracellular proteolysis. IN: Berlin RD, Herrmann M, Lepow IH and Tenzer JM (eds.) Molecular Basis of Biological Degradative Processes. Academic Press, New York, pp. 155–169, 1978.

    Google Scholar 

  46. Christman JK, Silverstein SC, Acs G: Plasminogen activators. IN: Barrett AJ (ed.) Proteinases in Mammalian Cells and Tissues. Elsevier/North Holland, Amsterdam, pp. 91–148, 1977.

    Google Scholar 

  47. Goldfarb RH: Plasminogen activators. Ann. Rep. Med. Chem. 18: 257–264, 1983.

    Article  CAS  Google Scholar 

  48. Goldfarb RH, Quigley JP: Production of plasminogen activator by chick embryo fibroblasts: Synergistic effect of Rous sarcoma virus transformation and treatment with the tumor promoter phorbol myristate acetate. Cancer Res. 38: 4601–4608, 1978.

    PubMed  CAS  Google Scholar 

  49. Quigley JP, Goldfarb RH: Morphological changes induced by endogenous protease activity in cultures of phorbol ester treated RSV-transformed chick fibroblasts: Evidence for direct proteolytic activity of plasminogen activator. J. Cell Biol. 79: 73a, 1978

    Google Scholar 

  50. Quigley JP: Phorbol ester-induced morphological changes in transformed chick fibroblasts: Evidence for direct catalytic involvement of plasminogen activator. Cell 17: 131–141, 1979.

    Article  PubMed  CAS  Google Scholar 

  51. Quigley JP, Martin BM, Goldfarb RH, Scheiner CJ, Muller WD: Involvement of serine proteases in growth control and malignant transformation. Cold Spring Harbor Conf. Cell Proliferation 6: 219–238, 1979.

    CAS  Google Scholar 

  52. Quigley JP, Goldfarb RH, Scheiner CJ, O’Donnell-Tormey J, Yeo T: Transformed cell membranes and plasminogen activator. Prog. Clin. Biol. Res. 42: 773–795, 1980.

    Google Scholar 

  53. Zimmerman M, Quigley JP, Ashe B, Dorn C. Goldfarb RH, Troll W: A direct fluorescent assay for urokinase and normal and malignant tissue plasminogen activator: Kinetics and inhibitor profile. Proc. Natl. Acad. Sci. USA 75: 750–753, 1978.

    Article  PubMed  CAS  Google Scholar 

  54. Keski-Oja J, Vaheri A: The cellular target for the plasminogen activator, urokinase, in human fibroblasts-66,000 dalton protein. Biochim. Biophys. Acta 720: 141–148, 1982.

    Article  PubMed  CAS  Google Scholar 

  55. Gunzler WA, Steffens GJ, Otting F, Kim S-MA, Frankus E, Flohe L: The primary structure of high molecular weight urokinase from human urine: The complete amino acid sequence of the A chain. Hoppe-Seyler’s Z. Physiol. Chem. 363: 1155–1165, 1982.

    Article  CAS  Google Scholar 

  56. Pohl G, Kallstrom M, Bergsdorf N, Wallen P, Jornvall H: Tissue plasminogen activator: Peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences. Biochemistry 23: 3701–3707, 1984.

    Article  PubMed  CAS  Google Scholar 

  57. Strassburger W, Wollmer A, Pitts JE, Glover ID, Tickle IJ, Blundell TL, Steffens GJ, Gunzler WA, Otting F, Flohe L: Adaptation of plasminogen activator sequences to known protease structures. FEBS Lett. 157: 219–223, 1983.

    Article  PubMed  CAS  Google Scholar 

  58. Patthy L, Trexler M, Vali Z, Banyai L, Varadi A: Kringles: Modules specialized for protein binding. Homology of the gelatin-binding region of fibronectin with the kringle structures of proteases. FEBS Lett. 171: 131–136, 1984.

    Article  PubMed  CAS  Google Scholar 

  59. Gross JL, Krupp MN, Rifkin DB, Lane MD: Down-regulation of epidermal growth factor receptor correlates with plasminogen activator activity in A431 epidermoid carcinoma cells. Proc. Natl. Acad. Sci. USA 80: 2276–2280, 1983.

    Article  PubMed  CAS  Google Scholar 

  60. Lee L, Weinstein IB: Epidermal growth factor, like phorbol esters, induces plasminogen activator in HeLa cells. Nature (London) 274: 696–697, 1978.

    Article  CAS  Google Scholar 

  61. Jetten AM, Goldfarb RH: Action of epidermal growth factor and retinoids on anchorage-dependent and -independent growth of nontransformed rat kidney cells. Cancer Res. 43: 2094–2099, 1983.

    PubMed  CAS  Google Scholar 

  62. Quigley JP: Association of a protease (plasminogen activator) with a specific membrane fraction isolated from transformed cells. J. Cell Biol. 71: 472–486, 1976.

    Article  PubMed  CAS  Google Scholar 

  63. Wun T-C, Ossowski L, Reich E: A proenzyme form of human urokinase. J. Biol. Chem. 257: 7262–7268, 1982.

    PubMed  CAS  Google Scholar 

  64. Skriver L, Nielsen LS, Stephens R, Dane K: Plasminogen activator released as inactive proenzyme from murine cells transformed by sarcoma virus. Eur. J. Biochem. 124: 409–414, 1982.

    Article  PubMed  CAS  Google Scholar 

  65. Nielsen LS, Hansen JG, Skriver L, Wilson EL, Kaltoft K, Zeuther J, Dand K: Purification of zymogen to plasminogen activator from human glioblastoma cells by affinity chromatography with monoclonal antibody. Biochemistry 21: 6410–6415, 1982.

    Article  PubMed  CAS  Google Scholar 

  66. Andreasen PA, Nielsen LS, Grbndahl-Hansen J, Skriver L, Zeuthen J, Stephens RW, Dan K: Inactive proenzyme to tissue type plasminogen activator from human melanoma cells, identified after affinity purification with a monoclonal antibody. EMBO J. 3: 51–56, 1984.

    PubMed  CAS  Google Scholar 

  67. Levin E: Latent tissue plasminogen activator produced by human endothelial cells in culture: Evidence for an enzyme-inhibitor complex. Proc. Natl. Acad. Sci. USA 80: 6804–6808, 1983.

    Article  PubMed  CAS  Google Scholar 

  68. Vassalli J-D, Dayer J-M, Wohlwend A, Belin D: Concomitant secretion of pro-urokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages. J. Exp. Med. 159: 1653–1668, 1984.

    Article  PubMed  CAS  Google Scholar 

  69. Hoal EG, Wilson EL, Dowdie DB: The regulation of tissue plasminogen activator activity by human fibroblasts. Cell 34: 273–279, 1983.

    Article  PubMed  CAS  Google Scholar 

  70. Cwikel BJ, Barouski-Miller PA, Coleman PL, Gelehrter TD: Dexamethasone induction of an inhibitor of plasminogen activator in HTC hepatoma cells. J. Biol. Chem. 259: 6847–6851, 1984.

    PubMed  CAS  Google Scholar 

  71. Eaton DL, Scott RW, Baker JB: Purification of human fibroblast urokinase proenzyme and analysis of its regulation by proteases and protease nexin. J. Biol. Chem. 259: 6241–6247, 1984.

    PubMed  CAS  Google Scholar 

  72. Saksela O, Vaheri A, Schleuning W-D, Mignatti P, Barlati S: Plasminogen activators, activation inhibitors and alpha2- macroglobulin produced by cultured normal and malignant human cells. Int. J. Cancer 33: 609–616, 1984.

    Article  PubMed  CAS  Google Scholar 

  73. O’Donnell-Tormey J, Quigley JP: Detection and partial characterization of a chymostatin sensitive endopeptidase in transformed fibroblasts. Proc. Natl. Acad. Sci. USA 80: 344–348, 1983

    Article  PubMed  Google Scholar 

  74. O’Donnell-Tormey J, Quigley JP: Inhibition of plasminogen activator release from transformed chicken fibroblasts by a protease inhibitor. Cell 27: 85–95, 1981.

    Article  PubMed  Google Scholar 

  75. Goldfarb RH, Quigley JP: Purification of plasminogen activator from Rous sarcoma virus transformed chick embryo fibroblasts treated with the tumor promoter phorbol-12-myristate-13-acetate. Biochemistry 19: 5463–5471, 1980.

    Article  PubMed  CAS  Google Scholar 

  76. DePetro G, Vartio T, Salonen EM, Vaheri A, Barlati S: Tissue type plasminogen activator, but not urokinase, exerts transformation-enhancing activity. Int. J. Cancer 33: 563–567, 1984.

    Article  CAS  Google Scholar 

  77. Davies RL, Rifkin DB, Tepper R, Miller A, Kucherlapati R: A polypeptide secreted by transformed cells that modulates human plasminogen activator production. Science 221: 171–173, 1983.

    Article  PubMed  CAS  Google Scholar 

  78. Liu H-Y, Yang PP, Toledo DL, Mangel WF: Modulation of cell-associated plasminogen activator activity by cocultivation of a stem cell and its tumorigenic descendant. Mol. Cell. Biol. 4: 160–165, 1984.

    PubMed  CAS  Google Scholar 

  79. Yang N-S, Park C, Longley C, Furmanski P: Effect of the extra-cellular matrix of plasminogen activator isozyme activities of human mammary epithelial cells in culture. Mol. Cell. Biol. 3: 982–990, 1983.

    PubMed  CAS  Google Scholar 

  80. Miskin R, Reich E: Plasminogen activator: Induction of synthesis by DNA damage. Cell 19: 217–224, 1980.

    Article  PubMed  CAS  Google Scholar 

  81. Miskin R, Ben-Ishai R: Induction of plasminogen activator by UV light in normal and xeroderma pigmentosum fibroblasts. Proc. Natl. Acad. Sci. USA 78: 6236–6240, 1981.

    Article  PubMed  CAS  Google Scholar 

  82. Ben-Ishai R, Sharon R, Rothman M, Miskin R: DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light. Carcinogenesis 5: 357–362, 1984.

    Article  PubMed  CAS  Google Scholar 

  83. Meyn MS, Rossman T, Troll W: A protease inhibitor blocks SOS-functions in Escherichia coli: Antipain prevents lambda-repressor inactivation, ultraviolet mutagenesis, and filamentous growth. Proc. Natl. Acad. Sci. USA 74: 1152–1156, 1977.

    Article  PubMed  CAS  Google Scholar 

  84. Badman M, Villani G, Boiteux S, Defais M, Caillet-Fauquest P, Spadari S: On the mechanism and genetic control of mutagenesis induced by carcinogenic mutagens. IN: Hiatt HH, Watson JD and Winsten JA (eds.) Origins of Human Cancer. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 903–922, 1977.

    Google Scholar 

  85. Rohrlich ST, Rifkin DB: Proteases and cell invasion. Ann. Rep. Med. Chem. 14: 229–239, 1979.

    Article  Google Scholar 

  86. Skehan P, Friedman SJ: Malignant transformation: In vivomethods and in vitro correlates. IN: Cameron IL and Pool TB (eds.) The Transformed Cell. Academic Press, New York, pp. 8–65, 1981.

    Google Scholar 

  87. Mullins DE, Rohrlich ST: The role of proteinases in cellular invasiveness. Biochim. Biophys. Acta 695: 177–214, 1983.

    PubMed  CAS  Google Scholar 

  88. Werb A, Banda MJ, Jones PA: Degradation of connective tissue matrices by macrophages. I. Proteolysis of elastin, glycoproteins, and collagen by proteinases isolated from macrophages. J. Exp. Med. 152: 1340–1357, 1980.

    CAS  Google Scholar 

  89. Jones PA, Werb Z: Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture. J. Exp. Med. 152: 1527–1536, 1980.

    Article  PubMed  CAS  Google Scholar 

  90. Werb Z, Bainton DF, Jones PA: Degradation of connective tissue matrices by macrophages. III. Morphological and biochemical studies on extracellular, pericellular and intracellular events in matrix degradation by macrophages in culture. J. Exp. Med. 152: 1537–1553, 1980.

    Article  PubMed  CAS  Google Scholar 

  91. Jones PA, Scott-Burden T: Activated macrophages digest the extracellular matrix proteins produced by cultured cells. Biochem. Biophys. Res. Commun. 86: 71–77, 1979.

    Article  PubMed  CAS  Google Scholar 

  92. Chapman HA, Stone DL, Vavrin Z: Degradation of fibrin and elastin by intact human alveolar macrophages in vitro. Characterization of a plasminogen activator and its role in matrix degradation. J. Clin. Invest. 73: 806–815, 1984.

    Article  PubMed  CAS  Google Scholar 

  93. Jones PA, DeClerck YA: Destruction of extracellular matrices containing glycoproteins, elastin and collagen by metastatic human tumor cells. Cancer Res. 40: 3222–3227, 1980.

    PubMed  CAS  Google Scholar 

  94. Kramer RH, Vogel KG, Nicolson GL: Solubilization and degradation of subendothelial matrix glycoproteins and proteoglycans by metastatic tumor cells. J. Biol. Chem. 257: 2678–2686, 1982.

    PubMed  CAS  Google Scholar 

  95. Goldfarb RH, Liotta LA, Garbisa S: Degradation of basement membrane components: Effects of plasminogen activator, plasmin, and alpha thrombin. Proc. Am. Assoc. Cancer Res. 22: 59, 1981.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  97. Liotta LA, Goldfarb RH, Terranova VP: Cleavage of laminin by thrombin and plasmin: Alpha thrombin selectively cleaves the beta chain of laminin. Thromb. Res. 21: 663–673, 1981.

    Article  PubMed  CAS  Google Scholar 

  98. Werb Z, Mainardi C, Vater C, Harris ED: Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. N. Eng. J. Med. 296: 1017–1023, 1977.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  100. O’Grady R, Upfold LI, Stephens RW: Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator. Int. J. Cancer 28: 509–515, 1981.

    Article  PubMed  Google Scholar 

  101. Salo T, Liotta LA, Keski-Oja J, Turpeenniemi-Hujanen T, Tryggvason K: Secretion of basement membrane collagen degrading enzyme and plasminogen activator by transformed cells–role in metastasis. Int. J. Cancer 30: 669–673, 1982.

    Article  PubMed  CAS  Google Scholar 

  102. Sheela S, Barrett JC: In vitrodegradation of radiolabeled, intact basement membrane mediated by cellular plasminogen activator. Carcinogenesis 3: 363–369, 1982.

    Article  PubMed  CAS  Google Scholar 

  103. Laug WE, DeClerck YA, Jones PA: Degradation of the subendothelial matrix by tumor cells. Cancer Res. 43: 1827–1834, 1983.

    PubMed  CAS  Google Scholar 

  104. Bogenmann E, Jones PA: Role of plasminogen in matrix breakdown by neoplastic celle. J. Natl. Cancer Inst. 71: 1177–1182, 1983.

    PubMed  CAS  Google Scholar 

  105. Helsel M, Laug WE, Jones PA: Inhibition by bovine endothelial cells of degradation by HT-1080 fibrosarcoma cells of extra-cellular matrix proteins. J. Natl. Cancer Inst. 71: 1183–1187, 1983.

    Google Scholar 

  106. Sloane BF, Honn KV, Sadler JG, Turner WA, Kimpson JJ, Taylor JD: Cathepsin B activity in B16 melanoma cells: A possible marker for metastatic potential. Cancer Res. 42: 980–986, 1982.

    PubMed  CAS  Google Scholar 

  107. Salonen E-M, Zitting A, Vaheri A: Lamivin interacts with plasminogen and its tissue-type activator. FEBS Lett. 172: 29–32, 1984.

    Article  PubMed  CAS  Google Scholar 

  108. Quigley JP: Morphological alterations and degradative ability of RSV-transformed chick fibroblasts when cultured on the extra-cellular matrix produced by normal chick fibroblasts. Proc. Am. Assoc. Cancer Res. 24: 29, 1983.

    Google Scholar 

  109. Chen W-T, Olden K, Bernard BA, Chu F-F: Expression of transformation-associated protease(s) that degrade fibronectin at cell contact sites. J. Cell Biol. 98: 1546–1555, 1984.

    Article  PubMed  CAS  Google Scholar 

  110. Maciag T, Kadish J, Wilkins L, Stemerman MB, Weinstein R: Organizational behavior of human umbilical vein endothelial cells. J. Cell Biol. 94: 511–520, 1982.

    Article  PubMed  CAS  Google Scholar 

  111. Markus G: Plasminogen activators in malignant growth. IN: Davidson JF (ed.) Progress in Fibrinolysis, Churchill- Livingstone, Edinburgh, pp. 587–600, 1983.

    Google Scholar 

  112. Markus G: The role of hemostasis and fibrinolysis in the metastatic spread of cancer. Semin. Thromb. Hemostasis 10: 61–79, 1984.

    Article  CAS  Google Scholar 

  113. Duffy MJ, O’Grady P: Plasminogen activator and cancer. Eur. J. Cancer Clin. Oncol. 20: 577–582, 1984.

    Article  PubMed  CAS  Google Scholar 

  114. Berman M, Winthrop S, Ausprunk D, Rose J, Langer R, Gage J: Plasminogen activator (urokinase) causes vascularization of the cornea. Invest. Opthalmol. Vis. Sci. 22: 191–199, 1982.

    CAS  Google Scholar 

  115. Rifkin DB, Moscatelli D, Gross J, Jaffe E: Proteases, angiogenesis, and invasion. IN: Nicolson G and Milas L (eds.) Cancer Invasion and Metastasis: Biologic and Therapeutic Aspects Raven Press, New York, pp. 187–200, 1984.

    Google Scholar 

  116. Glaser BM, Kalebic T, Garbisa S, Connor TB, Liotta LA: Degradation of basement membrane components by vascular endothelial cells: Role in neovascularization. IN: Wolpert L (ed.) Development of the Vascular System(Ciba Foundation Symposium 100), Pitman Books Ltd., London, pp. 150–162, 1983.

    Google Scholar 

  117. Bruesch MR, Johnson GL, Palackdharry CS, Weber MJ, Carl PL: Plasminogen activator in normal and tumor-bearing mice. Int. J. Cancer 32: 121–126, 1983.

    Article  PubMed  CAS  Google Scholar 

  118. Nicolson GL, Winkelhake JL, Nussey AC: An approach to studying the cellular properties associated with metastasis: Some in vitroproperties of tumor variants selected in vivo for enhanced metastasis. IN: Weiss L (ed.) Fundamental Aspects of Metastasis North Holland Publishing Co., Amsterdam, pp. 291–303, 1976.

    Google Scholar 

  119. Roblin R: Contributions of secreted tumor cell products to metastasis. Cancer Biol. Rev. 2:59–94, 1981.

    Google Scholar 

  120. Talmadge JE, Starkey JR, Stanford DR: In vitro characteristics of metastatic variant subclones of restricted genetic origin. J. Supramol. Struc. Cell. Biochem. 15: 139–151, 1981.

    Article  CAS  Google Scholar 

  121. Whur P, Magudia M, Boston J, Lockwood J, Williams DC: Plasminogen activator in cultured Lewis lung carcinoma cells measured by chromogenic aubstrate assay. Br. J. Cancer 42: 305–313, 1980.

    Article  PubMed  CAS  Google Scholar 

  122. Coen D, Bottazzi B, Bini A, Conforti MG, Mantovani A, Mussoni L, Donati MB: Plasminogen activator activity of metastatic variants from a murine fibrosarcoma: Effect of thrombin in vitro. Int. J. Cancer 32: 67–70, 1983.

    Article  PubMed  CAS  Google Scholar 

  123. Giraldi T, Sava G, Kopitar M, Suhar A, Turk V, Baici A: Methodologic problems encountered in the assay of proteinases in Lewis lung carcinoma, a mouse metastasizing tumor. Tumori 68: 381–387, 1982.

    PubMed  CAS  Google Scholar 

  124. McLaughlin MEH, Liener IE, Wang N: Proteolytic and metastatic activities of clones derived from a methylcholanthrene induced murine fibrosarcoma. Clin. Exp. Metastasis 1: 359–371, 1983.

    Article  PubMed  CAS  Google Scholar 

  125. Lowe FC, Isaacs JT: Biochemical methods for predicting metastatic ability of prostatic cancer utilizing the Dunning R-3327 rat prostatic adenocarcinoma system as a model. Cancer Res. 44: 744–752, 1984.

    PubMed  CAS  Google Scholar 

  126. Wang BS, McLoughlin GA, Richie JP, Mannick JA: Correlation of the production of plasminogen activator with tumor metastasis in B16 melanoma cell lines. Cancer Res. 40: 288–292, 1980.

    PubMed  CAS  Google Scholar 

  127. Pollard M, Luckert PH, Bruckner-Kardoss E: The association of plasminogen activator (PLA) with metastatic spread of rat prostate adenocarcinoma. Fed. Proc. Fed. Am. Soc. Exp. Biol. 42: 773, 1983.

    Google Scholar 

  128. Ng R, Kellen JA, Wong ACH: Plasminogen activators as markers of tumor colonization potential. Invasion Metastasis 3: 243–248, 1983

    PubMed  CAS  Google Scholar 

  129. Ramshaw IA, Carlsen S, Wang HC, Badenoch-Jones P: The use of cell fusion to analyze factors involved in tumor cell metastasis. Int. J. Cancer 32: 471–478, 1983.

    Article  PubMed  CAS  Google Scholar 

  130. Carlsen SA, Ramshaw IA, Warrington RC: Involvement of plasminogen activator production with tumor metastasis in a rat model. Cancer Res. 44: 3012–3016, 1984.

    CAS  Google Scholar 

  131. Skriver L, Larsson L-I, Kielberg V, Nielsen LS, Andresen PB, Kristensen P, Danφ K: Immunocytochemical localization of urokinase-type plasminogen activator in Lewis lung carcinoma. J. Cell Biol. 99: 752–757, 1984.

    Article  Google Scholar 

  132. Tanaka N, Ogawa H, Tanaka K, Kinjo M, Kohga S: Effects of tranexamic acid and urokinase on hematogenous metastases of Lewis lung carcinoma in mice. Invasion Metastasis 1: 149–157, 1981.

    PubMed  CAS  Google Scholar 

  133. Ossowski L, Reich E: Experimental model for quantitative study of metastasis. Cancer Res. 40: 2300–2309, 1980.

    PubMed  CAS  Google Scholar 

  134. Ossowski L, Reich E: Antibodies to plasminogen activator inhibit tumor metastasis. Cell 35: 611–619, 1983.

    Article  PubMed  CAS  Google Scholar 

  135. Friedman EA: Differential response of premalignant epithelial cell classes to phorbol ester tumor promoters and to deoxycholic acid. Cancer Res. 41: 4588–4599, 1981.

    PubMed  CAS  Google Scholar 

  136. Friedman E, Urmacher C, Winawer S: A model for human colon carcinoma evolution based on the differential response of cultured preneoplastic, premalignant, and malignant cells to 12-Otetradecanoylphorbol-13-acetate. Cancer Res. 44: 1568–1578, 1984.

    PubMed  CAS  Google Scholar 

  137. Friedman E, Verderame M, Winawer S, Pollack R: Actin cytoskeletal organization loss in the benign-to-malignant tumor transition in cultured human colonic epithelial cells. Cancer Res. 44: 3040–3050, 1984.

    PubMed  CAS  Google Scholar 

  138. Corasanti JG, Celik C, Camiolo SM, Mittelman A, Evers JL, Barbasch A, Hobika GH, Markus G: Plasminogen activator content of human colon tumors and normal mucosae: Separation of enzymes and partial purification. J. Natl. Cancer Inst. 65: 345–351, 1980.

    PubMed  CAS  Google Scholar 

  139. Markus G, Camiolo SM, Kohga S, Madeja JM, Mittelman A: Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic tumors. Cancer Res. 43: 5517–5525, 1983.

    PubMed  CAS  Google Scholar 

  140. Camiolo SM, Markus G, Englander LS, Siuta M, Hobika GH, Kohga S: Plasminogen activator content and secretion in explants of neoplastic and benign human prostate tissues. Cancer Res. 44: 311–318, 1984.

    PubMed  CAS  Google Scholar 

  141. Markus G, Kohga S, Camiolo SM, Madeja JM, Ambrus JL, Karakousis C: Plasminogen activators in human malignant melanoma. J. Natl. Cancer Inst. 72: 1213–1222, 1984.

    PubMed  CAS  Google Scholar 

  142. Colombi M, Barlati S, Magdelenat H, Fiszer-Szafarz B: Relationship between multiple forms of plasminogen activator in human breast tumors and plasma and the presence of metastases in lymph nodes. Cancer Res. 44: 2971–2975, 1984.

    PubMed  CAS  Google Scholar 

  143. Abecassis J, Collard R, Eber M, Pusel J, Fricker JP, Methlin G: Proteinases and sialyltransferase in human breast tumors. Int. J. Cancer 33: 821–824, 1984.

    Article  PubMed  CAS  Google Scholar 

  144. Stephens RW, Golder JP: Novel properties of human monocyte plasminogen activator. Eur. J. Biochem. 139: 253–258, 1984.

    Article  PubMed  CAS  Google Scholar 

  145. Goldfarb RH, Timonen T, Herberman RB: Production of plasminogen activator by human natural killer cells: Large granular lymphocytes. J. Exp. Med. 159: 935–951, 1984.

    Article  PubMed  CAS  Google Scholar 

  146. Nicolson GL, Irimura T, Nakajima N, Estrada J: Metastatic cell attachment to and invasion of vascular endothelium and its underlying basal lamina using endothelial cell monolayers. IN: Nicolson GL and Milas (eds.) Cancer Invasion and Metastasis: Biologic and Therapeutic Aspects Raven Press, New York, pp. 145–167, 1984.

    Google Scholar 

  147. Nicolson GL: Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J. Histochem. Cytochem. 30: 214–220, 1982.

    Article  PubMed  CAS  Google Scholar 

  148. Vlodaysky I, Ariav Y, Atzmon R, Fuks Z: Tumor cell attachment to the vascular endothelium and subsequent degradation of the subendothelial extracellular matrix. Exp. Cell Res. 140: 149–159, 1982

    Article  Google Scholar 

  149. Nakajima M, Irimura T, DiFerrante D, DiFerrante N, Nicolson GL: Heparan sulfate degradation: Relation to tumor invasive and metastatic properties of mouse B16 melanoma sublines. Science 220: 611–613, 1983.

    Article  PubMed  CAS  Google Scholar 

  150. Kramer RH, Vogel KG: Selective degradation of basement membrane macromolecules by metastatic melanoma cells. J. Natl. Cancer Inst. 72: 889–899, 1984.

    PubMed  CAS  Google Scholar 

  151. Nakajima M, Irimura T, DiFerrante N, Nicolson GL: Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase. J. Biol. Chem. 259: 2283–2290, 1984.

    PubMed  CAS  Google Scholar 

  152. Vlodaysky I, Fuks Z, Bar-Ner M, Ariav Y, Schirrmacher V: Lymphoma cell-mediated degradation of sulfated proteoglycans in the subendothelial extracellular matrix: Relationship to tumor cell metastasis. Cancer Res. 43: 2704–2711, 1983.

    Google Scholar 

  153. Savion N, Vlodaysky I, Fuks Z: Interaction of T lymphocytes and macrophages with cultured vascular endothelial cells: Attachment, invasion and subsequent degradation of the subendothelial matrix. J. Cell. Physiol. 118: 169–178, 1984.

    Article  PubMed  CAS  Google Scholar 

  154. Woodley DT,Rao CN, Hassell JR, Liotta LA, Martin GR, Kleinman HK: Interactions of basement membrane components. Biochim. Biophys. Acta 761:278–283, 1983.

    Google Scholar 

  155. Hedman K, Vartlo T, Johansson S, Kjellen L, Hook M, Linker A, Salonen M, Vaheri A: Integrity of the pericellular fibronectin matrix of fibroblasts is independent of sulfated glycosaminoglycans. EMBO J. 3: 581–584, 1984.

    PubMed  CAS  Google Scholar 

  156. Iozzo RV: Biosynthesis of heparan sulfate proteoglycan by human colon carcinoma cells and its localization at the cell surface. J. Cell Biol. 99: 403–417, 1984.

    Article  PubMed  CAS  Google Scholar 

  157. Luikart SD, Maniglia CA, Sartorelli AC: Influence of collagen substrata on glycosaminoglycan production by B16 melanoma cells. Proc. Natl. Acad. Sci. USA 80: 3738–3742, 1983.

    Article  PubMed  CAS  Google Scholar 

  158. Lark MW, Culp LA: Multiple classes of heparan sulfate proteoglycans from fibroblast substratum adhesion sites. Affinity fractionation on columns of platelet factor 4, plasma fibronectin, and octyl-Sepharose. J. Biol. Chem. 259: 6773–6782, 1984.

    PubMed  CAS  Google Scholar 

  159. Gallagher JT, Hampson IN: Proteoglycans in cellular differentiation and neoplasia. Biochem. Soc. Trans. 12: 541–543, 1984.

    PubMed  CAS  Google Scholar 

  160. Sloane BF, Honn KV, Sadler JG, Turner WA, Kimpson JJ, Taylor JD: Cathepsin B activity in B16 melanoma cells: A possible marker for metastatic potential. Cancer Res. 42: 980–986, 1982.

    PubMed  CAS  Google Scholar 

  161. Sloane BF, Dunn JR, Honn KV: Lysosomal cathepsin B: Correlation with metastatic potential. Science 212: 1151–1153, 1981.

    Article  PubMed  CAS  Google Scholar 

  162. Poole AR, Tiltman KJ, Recklies AD, Stoker TAM: Differences in secretion of the proteinase cathepsin B at the edges of human breast carcinomas and fibroadenomas. Nature (London) 273: 545–547, 1978.

    Article  CAS  Google Scholar 

  163. Recklies AD, Tiltman KJ, Stoker TAM, Poole AR: Secretion of proteinases from malignant and nonmalignant human breast tissue. Cancer Res. 40: 550–556, 1980.

    PubMed  CAS  Google Scholar 

  164. Pietras RJ, Szego CM, Mangan CE, Seeler BJ, Burtnett MM: Elevated serum cathepsin B1-like activity in women with neoplastic disease. Gynecol. Oncol. 7: 1–17, 1979.

    Article  PubMed  CAS  Google Scholar 

  165. Recklies AD, Mort JS, Poole AR: Secretion of a thiol proteinase from mouse mammary carcinomas and its characterization. Cancer Res. 42: 1026–1032, 1982.

    PubMed  CAS  Google Scholar 

  166. Pietras RJ, Roberts JA: Cathepsin B-like enzymes: Subcellular distribution and properties in neoplastic and control cells from human ectocervix. J. Biol. Chem. 256: 8536–8544, 1981.

    PubMed  CAS  Google Scholar 

  167. Mort JS, Leduc MS, Recklies AD: Characterization of a latent cysteine proteinase from ascitic fluid as a high molecular weight form of cathepsin B. Biochim. Biophys. Acta 755: 369–375, 1983.

    PubMed  CAS  Google Scholar 

  168. Honn KV, Cavanaugh P, Evens C, Taylor JD, Sloane BF: Tumor cell-platelet aggregation: Induced by cathepsin B-like proteinase and inhibited by prostacyclin. Science 217: 540–542, 1982.

    Article  PubMed  CAS  Google Scholar 

  169. Cavanaugh PG, Sloane BF, Bajkowski AS, Gasic GJ, Gasic TB, Honn KV: Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. Clin. Exp. Metastasis 1: 297–307, 1983.

    Article  PubMed  CAS  Google Scholar 

  170. Lesser M, Chang JC, Orlowski J, Kilburn K, Orlowski M: Cathepsin B and prolyl endopeptidase activity in peritoneal and alveolar macrophages. J. Lab. Clin. Med. 101: 327–334, 1983.

    PubMed  CAS  Google Scholar 

  171. Gilbert LC, Gordon SG: Relationship between cellular procoagulant activity and metastatic activity of B16 melanoma variants. Cancer Res. 43: 536–540, 1983.

    PubMed  CAS  Google Scholar 

  172. Dvorak HF, Van DeWater L, Bitzer AM, Dvorak AM, Anderson D, Harvey VS, Bach R, Davis GL, DeWolf W, Carvalho CA: Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells. Cancer Res. 43: 4334–4342, 1983.

    Google Scholar 

  173. Gordon SG, Franks JJ, Lewis B: Cancer procoagulant A: A factor X activating procoagulant from malignant tissue. Thromb. Res. 6: 127–137, 1975.

    Article  PubMed  CAS  Google Scholar 

  174. Colucci M, Giavazzi M, Allesandri G, Semeraro N, Mantovani A, Donati MB: Procoagulant activity of sarcoma sublines with different metastatic potential. Blood 57: 733–735, 1981.

    PubMed  CAS  Google Scholar 

  175. Liotta LA, Foidart JM, Gehon Robey P, Martin GR, Gullino PM: Identification of micrometastasis of breast carcinomas by presence of basement membrane collagen. Lancet 2: 146–147, 1979.

    Article  PubMed  CAS  Google Scholar 

  176. Siegal GP, Barsky SH, Terranova VP, Liotta LA: Stages of neoplastic transformation of human breast tissue as monitored by dissolution of basement membrane components. Invasion Metastasis 1: 54–70, 1981.

    PubMed  CAS  Google Scholar 

  177. Bettelheim R, Mitchell D, Gusterson BA: Immunocytochemistry in the identification of vascular invasion in breast cancer. J. Clin. Pathol. 37: 364–366, 1984.

    Article  PubMed  CAS  Google Scholar 

  178. Ekblom P, Miettinen M, Foreman L, Andersson L: Basement membrane and apocrine epithelial antigens in differential diagnosis between tubular carcinoma and sclerosing adenosis of the breast. J. Clin. Pathol. 37: 357–363, 1984.

    Article  PubMed  CAS  Google Scholar 

  179. Burtin P, Chavanel G, Foidart JM, Andre J: Alterations of the basement membrane and connective tissue antigens in human metastatic lymph nodes. Int. J. Cancer 31: 719–726, 1983.

    Article  PubMed  CAS  Google Scholar 

  180. Barsky SH, Togo S, Garbisa S, Liotta LA: Type IV collagenase immunoreactivity in invasive breast carcinoma. Lancet 1: 296–297, 1983

    Article  PubMed  CAS  Google Scholar 

  181. Wilson EL, Jacobs P, Dowdle EB: The secretion of plasminogen activators by human myeloid leukemic cells in vitro. Blood 61: 568–574, 1983.

    PubMed  CAS  Google Scholar 

  182. Nelles LP, Schnebli HP: Are proteinase inhibitors potentially useful in tumor therapy? Invasion Metastasis 2: 113–124, 1982.

    PubMed  CAS  Google Scholar 

  183. Giraldi T, Sava G: Selective antimetastatic drugs (review). Anticancer Res. 1: 163–174, 1981.

    PubMed  CAS  Google Scholar 

  184. Weiss L, Ward PM: Cell detachment and metastasis. Cancer Metastasis Rev. 2: 111–127, 1983.

    Article  PubMed  CAS  Google Scholar 

  185. Carl PL, Chakravarty PK, Katzenellenbogen JA, Weber MJ: Protease-activated “prodrugs” for cancer chemotherapy. Proc. Natl. Acad. Sci. USA 77: 2224–2228, 1980.

    Article  PubMed  CAS  Google Scholar 

  186. Chakravarty PK, Carl PL, Weber MJ, Katzenellenbogen JA: Plasminactivated prodrugs for cancer chemotherapy. 2. Synthesis and biological activity of peptidyl derivatives of doxorubicin. J. Med. Chem. 26: 638–644, 1983.

    Article  PubMed  CAS  Google Scholar 

  187. Iwakawa A, Tanaka K: Effect of fibrinolysis inhibitor and chemotherapeutics on the growth of human cancers transplanted into nude mice and in tissue culture. Invasion Metastasis 2: 232–248, 1982

    PubMed  CAS  Google Scholar 

  188. Sundbeck A, Myrhage R, Peterson H-I: Influence of tranexamic acid on tumor vascularization. An experimental microangiographic study. Anticancer Res. 1: 295–298, 1981.

    PubMed  CAS  Google Scholar 

  189. Astedt B, Glifberg I, Mattsson W, Trope T: Arrest of growth of ovarian tumor by tranexamic acid. J. Am. Med. Assoc. 238: 154–155, 1977.

    Article  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Martinus Nijhoff Publishing, Boston

About this chapter

Cite this chapter

Goldfarb, R.H. (1986). Proteolytic Enzymes in Tumor Invasion and Degradation of Host Extracellular Matrices. In: Honn, K.V., Powers, W.E., Sloane, B.F. (eds) Mechanisms of Cancer Metastasis. Developments in Oncology, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2635-9_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-2635-9_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9646-1

  • Online ISBN: 978-1-4613-2635-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Navigation