Summary
Connective tissue stroma and basement membrane structures probably present natural barriers to the migration of tumor cells. It has therefore been proposed that collagenolytic enzymes are required to facilitate the spread and invasion of tumor cells into host tissues. The collagenases and cathepsin B-like enzymes are thought to be involved, but the cellular source of collagenolytic activity at the tumor: host interface or invasion zone' remains obscure in most cases. The ‘invasion zone’ of different tumors is very variable with regard to the type and numbers of host or tumor cells, as well as the type of collagenous matrix, and few generalities can be made. The existence within a tumor of specialised subpopulations of cells which have different metastatic potential has been postulated. As a consequence it seems plausible that the phenotypic expression of highly invasive or metastatic tumor cells should include the potential for generating collagenolytic activity. Immunolocalisation studies have demonstrated the production of type I and type IV collagenases at sites of tumor invasion, but it does not appear to be a continuous process and only a small proportion of tumor and/or host cells elaborate enzyme at any one moment. Collagenase production is invariably microenvironmental in nature and it seems likely that local host:tumor cell interactions are important in modulating collagenolysis. Macrophages and mast cells have been shown to stimulate collagenase expression by tumor and stromal cells in vitro, and it is proposed that these cells may assume a contributory role for the induction of collagenolytic activity in vivo. The collagenolytic mechanisms that operate at micro-foci of host:tumor junctions probably depend upon the type of collagen, the cellular composition and the extracellular ionic conditions of each invasion site. Either tumor or host cells may elaborate enzymes, this being dependent upon the type and/or tissue location of the invasive tumor.
Similar content being viewed by others
References
Piez KA: Molecular and aggregate structures of the collagens. In: Piez KA, Reddi AH (eds) Extracellular Matrix Biochemistry. Elsevier, New York, 1984, pp 1–39.
Miller EJ: Chemistry of the collagens and their distribution. In: Piez KA, Reddi AH (eds) Extracellular Matrix Biochemistry. Elsevier, New York, 1984, pp 41–82.
Gross J, Highberger JH, Johnson-Wint B, Biswas C: Mode of action and regulation of tissue collagenases. Woolley DE, Evanson JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, Chichester, pp 11–35, 1980.
Woolley DE: Mammalian collagenases. In: Piez KA, Reddi AH (eds) Extracellular Matrix Biochemistry. Elsevier, New York, 1984, pp 119–157.
Woolley DE, Taylor DJ, Yoffe JR: Mammalian collagenases: aspects of regulation. Life Chemistry Reports 2: 181–235, 1984.
Gadek JE, Fells GA, Wright DG, Crystal RG: Human neutrophil elastase functions as a type III collagen ‘collagenase’. Biochem Biophys Res Commun 95: 1815–1822, 1980.
Liotta LA, Thorgeirsson UP, Garbisa S: role of collagenases in tumor cell invasion. Cancer Metastasis Rev 1: 277–288, 1982.
Murphy G, Cawston TE, Galloway WA, Barnes MJ, Bunning RAD, Mercer E, Reynolds JJ, Burgeson RE: Metalloproteinases from rabbit bone culture medium degrades type IV and V collagens, laminin and fibronectin. Biochem J 199: 807–811, 1981.
Sage H, Bornstein P: Characterisation of a novel collagen chain in human placenta and its relation to the AB collagen. Biochemistry 18: 3815–3822, 1979.
Uitto V-J, Schwartz D, Veis A: Degradation of basement membrane collagen by neutral proteases from human granulocytes. Eur J Biochem 105: 409–417, 1980.
Vaes G: Collagenase, lysosomes and osteoclastic bone resorption. In: Woolley DE, Evanson JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, Chichester, pp 185–208, 1980.
Woolley DE: Proteolytic enzymes of invasive cells. Mareel MM, Calman KC (eds) Invasion: experimental and clinical implications, Oxford University Press, Oxford, pp 228–251, 1985.
Woolley DE, Tetlow LC, Evanson JM: Collagenase immunolocalisation studies of rheumatoid and malignant tissues. In: Woolley DE, Evanson JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, Chichester, pp 105–125, 1980.
Woolley DE, Tetlow LC, Mooney CJ, Evanson JM: Human collagenase and its natural inhibitors in relation to tumor invasion. In: Strauli P, Barrett JC, Baici A (eds) Proteinases in tumour invasion. EORTC Monograph Vol 6. Raven Press, New York, pp 97–115, 1980.
Horwitz AL, Hance AJ, Crystal RG: Granulocyte collagenase: selective digestion of type I relative to type III collagen. Proc Natl Acad Sci USA 74: 897–901, 1977.
Oyomada I, Kitaoka M, Araki R, Yoshioka H, usuku G: Collagenase from the culture medium of rabbit colon wall with special reference to the latent type and substrate susceptibility. Gastroenterology 85: 376–383, 1983.
Woolley DE: Human Collagenases: comparative and immunolocalisation studies. Ciba Found Symp 75: 69–86, 1979.
Liotta LA, Tryggvason K, Garbisa S, Gehron-Robey P, Abe S: Partial purification and characterization of a neutral protease which cleaves type IV collagen. Biochemistry 20: 100–104, 1981.
Salo T, Liotta LA, Tryggvason K: Purification and characterisation of a murine basement membrane collagen-degrading enzyme secreted by metastatic tumor cells. J Biol Chem 258: 3058–3063, 1983.
Woolley DE: Collagenase immunolocalization studies of human tumours. In: Liotta LA, Hart IR (eds) Tumor invasion and metastasis. Martinus Nijhoff, The Hague, pp 391–404, 1982.
Barsky SH, Togo S, Garbisa S, Liotta LA: Type IV collagenase immunoreactivity in invasive breast carcinoma. Lancet 1: 296–297, 1983.
Bauer EA, Gordon JM, Reddick ME, Eisen AZ: Quantitation and immunocytochemical localisation of human skin collagenase in basal cell carcinoma. J Invest Dermatol 69: 363–367, 1977.
Thorgeirsson UP, Liotta LA, Kalebic T, Marguiles IM, Thomas K, Rios-Candelore M, Russo RG: Effect of natural protease inhibitors and a chemoattractant on tumor cell invasion in vitro. J Natl Cancer Inst 69: 1049–1054, 1982.
Woolley DE, Grafton CA: Collagenase immunolocalisation studies of cutaneous secondary melanomas. Br J Cancer 42: 260–265, 1980.
Russo RG, Thorgeirsson UP, Liotta LA: In vitro quantitative assay of invasion using human amnion. In: Liotta LA, Hart IR (eds) Tumor Invasion and metastases. Martinus Nijhoff, The Hague, pp 173–187, 1982.
Tarin D, Hoyt BJ, Evans DJ: Correlation of collagenase secretion with metastatic-colonization potential in naturally occurring murine mammary tumors. Brit J Cancer 46: 266–278, 1982.
Paranjpe M, Engel L, Young N, Liotta LA: Activation of breast carcinoma collagenase through plasminogen activator. Life Sci 26: 1223–1231, 1980.
Moscatelli D, Rifkin DB, Isseroff RR, Jaffe EA: Plasminogen activator, plasmin and collagenase interactions. In: Strauli P, Barrett AJ, Baici A (eds) Proteases and tumor invasion. EORTC Monograph Vol. 6. Raven Press, New York, pp 143–152, 1980.
Goldfarb RH: Proteases in tumor invasion and metastasis. Liotta LA, Hart IR (eds) Tumor invasion and metastasis. Martinus Nijhoff, The Hague, pp 375–390, 1982.
Recklies AD, Tiltman KJ, Stoker AM, Poole AR: Secretion of proteinases from malignant and nonmalignant human breast tissue. Cancer Res 40: 550–556, 1980.
Salo T, Liotta LA, Keski-Oja J, Turpeenniemi-Hujanen T, Tryggvason K: Secretion of basement membrane collagendegrading enzyme and plasminogen activator by transformed cells-role in metastasis. Int J Cancer 30: 669–673, 1982.
Steven FS, Griffin MM, Itzhaki S, Al-Habib A: A trypsinlike neutral proteinase on Ehrlich ascites cell surfaces: its role in the activation of tumor-cell zymogen of collagenase. Brit J Cancer 42: 712–721, 1980.
Short AK, Steven FS, Griffin MM, Itzhaki S: B-Naphthylamidase activity of the cell surface of Ehrlich ascites cells. Reversible control of enzyme activity by metal ions and thiols. Brit J Cancer 44: 709–716, 1981.
DiStefano JF, Beck G, Lane B, Zucker S: Role of tumor cell membrane-bound serin proteases in tumor-induced target cytolysis. Cancer Res 42: 207–218, 1982.
Etherington DJ: Proteinases in connective tissue breakdown. Ciba Found Symp 75: 87–103, 1979.
Kirschke H, Kembhavi AA, Bohley P, Barrett AJ: Action of rat liver cathepsin L on collagen and other substrates. Biochem J 201: 367–372, 1982.
Recklies AD, Poole AR: Proteolytic mechanisms of tissue destruction in tumor growth and metastasis. In: Weiss L, Gilbert HA (eds) Liver Metastasis, GK Hall, Boston, pp 77–95, 1982.
Mort JS, Leduc MS, Recklies AD: A latent thiol proteinase from ascitic fluid of patients with neoplasia. Biochim Biophys Acta 662: 173–180, 1981.
Mort JS, Leduc MS, Recklies AD: Characterisation of a latent cysteine proteinase from ascitic fluid as a high molecular weight form of cathepsin B. Biochim Biophys Acta 755: 369–375, 1983.
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 273: 545–547, 1978.
Poole AR, Recklies AD, Mort JS: Secretion of proteinases from human breast tissues: excessive release from carcinomas of a thiol proteinase. In: Strauli P, Barrett AJ, Baici A (eds) Proteinases in tumor invasion. EORTC' monograph. Vol 6. Raven Press, New York, pp 81–93, 1980.
Sylven B: Cellular detachment by purified lysosomal cathepsin B. Eur J Cancer 4: 559–562, 1968.
Burleigh PMC, Barrett AJ, Lazarus GS: Cathepsin B1. A lysosomal enzyme that degrades native collagen. Biochem J 137: 387–398, 1974.
Eeckhout Y, Vaes G: Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin, and kallikrein, and spontaneous activation. Biochem J 166: 21–31, 1977.
Sylven B: Biochemical and enzymatic factors involved in cellular detachment. In: Garattini S, Frachi G (eds) Chemotherapy of cancer dissemination and metastasis. Raven Press, New York, pp 129–138, 1973.
Pietras RJ, Szego CM, Mangan CE, Seeler BJ, Burtnett MM: Elevated serum cathepsin B1-like activity in women with neoplastic disease. Gyn Oncol 7: 1–17, 1979.
Benitez-Bribiesca L, Preyre-Horta R, Gallegos-Vargas G, Huerta-Sanchez R, Alfaro-Aceves L: Cathepsin B and antiproteinases in patients with carcinoma of the cervix. Arch Invest Med (Mex) 12: 517–521, 1981.
Bosman HB, Hall TC: Enzyme activity in invasive tumors of human breast and colon. Proc Natl Acad Sci USA 71: 1833–1837, 1974.
Sloane BF, Dunn JR, Honn KV: Lysosomal cathepsin B: Correlation with metastatic potential. Science 212: 1151–1153, 1981.
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.
Recklies AD, Poole AR, Mort JS: A cysteine proteinase secreted from human breast tumors is immunologically related to cathepsin B, Biochem J 207: 633–636, 1982.
Olstein AD, Leiner IE: Comparative studies of mouse liver cathepsin B and an analogous tumor thiol proteinase. J Biol Chem 258: 11049–11056, 1983.
Graf M, Baici A, Strauli P: Histochemical localisation of cathepsin B at the invasion front of the rabbit V2 carcinoma. Lab Invest 45: 587–596, 1981.
Strauli P: A concept of invasion. In: Strauli P, Barrett AJ, Baici A (eds) Proteinases and tumour invasion. EORTC Monograph series. Vol 6. Raven Press, New York, pp 1–15, 1980.
Tarin D: Cellular interactions in neoplasia. In: Weiss L (ed) Fundamental aspects of metastasis. North Holland, Amsterdam, pp 151–187, 1976.
Biswas C: Host-tumor cell interactions and collagenase activity. Liotta LA, Hart IR (eds) Tumor invasion and metastasis. Martinus Nijhoff, The Hague, pp 405–425, 1982.
Henry N, Eeckhout Y, van Lamsweerde AL, Vaes G: Co-operation between metastatic tumor cells and macrophages in the degradation of basement membrane (type IV) collagen. FEBS Lett 161: 243–246, 1983.
Henry N, van Lamsweerde AL, Vaes G: Collagen degradation by metastatic variants of Lewis lung carcinoma: co-operation between tumor cells and macrophages. Cancer Res 43: 5321–5327, 1983.
Yoffe JR, Taylor DJ, Woolley DE: Mast cell products stimulate collagenase and prostaglandin E production by cultures of adherent rheumatoid synovial cells. Biochem Biophys Res Commun 122: 270–276, 1984.
Wood GW, Gillespie GY: Studies on the role of macrophages in regulation of growth and metastasis of murine chemically-induced fibrosarcomas. Int J Cancer 16: 1022–1027, 1975.
Wood GW, Gollahon KA: Detection and quantitation of macrophage infiltration into primary human tumors with the use of cell-surface markers. J Natl Cancer Inst 59: 1081–1089, 1977.
Svennerig JL, Lovik M, Svaar H: Isolation and characterisation of lymphocytes and macrophages from solid, malignant, human tumors. Int J Cancer 23: 626–631, 1979.
Dayer JM, Goldring SR, Robinson DR, Krane SM: Cell-cell interactions and collagenase production. In: Woolley DE, Evanson JM (eds) Collagenase in normal and pathological connective tissues. John Wiley & Sons, Chichester, pp 83–104, 1980.
Laub R, Huybrechts-Godin G, Peeters-Joris C, Vaes G: Degradation of collagen and proteoglycan by macrophages and fibroblasts. Individual potentialities of each cell type and cooperative effects through activation of macrophages. Biochim Biophys Acta 74: 425–433, 1982.
Deshmukh-Phadke K, Lawrence M, Nanda S: Synthesis of collagenase and neutral proteases by articular chondrocytes: Stimulation by a macrophage-derived factor. Biochem Biophys Res Commun 85: 490–496, 1978.
Pepys J, Edwards AM (eds) The mast cell: its role in health and disease. Pitman Medical, London, 1979.
Birkedal-Hansen H, Cobb CM, Taylor RE, Fullmer HM: Activation of fibroblast procollagenase by mast cell proteinases. Biochim Biophys Acta 438: 273–286, 1976.
Yoffe JR, Taylor DJ, Woolley DE: Mast cell heparin stimulates the production of mononuclear cell factor by human monocyte-macrophages. Biochem J (In press).
Bauer EA, Uitto J, Walters RC, Eisen AZ: Enhanced collagenase production by fibroblasts derived from human basal cell carcinomas. Cancer Res 39: 4594–4599, 1979.
Biswas C: Tumor cell stimulation of collagenase production by fibroblasts. Biochem Biophys Res Commun 109: 1026–1034, 1982.
Biswas C, Bloch KJ, Gross J: Collagenolytic activity of rabbit V2 carcinoma implanted in the nude mouse. J Natl Cancer Inst 69: 1329–1326, 1982.
Poste G, Fidler IJ: The pathogenesis of cancer metastasis. Nature 283: 139–146, 1980.
Hart IR, Fidler IJ: Cancer invasion and metastasis. Quart Rev Biol 55: 121–142, 1980.
Reynolds JJ, Bunning RAD, Cawston TE, Murphy G: Tissue metallo-proteinase inhibitors and their role in matrix catabolism. In: Dingle JT, Gordon JL (eds) Cellular Interactions. Elsevier/North Holland, Amsterdam, pp 205–214, 1981.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Woolley, D.E. Collagenolytic mechanisms in tumor cell invasion. Cancer Metast Rev 3, 361–372 (1984). https://doi.org/10.1007/BF00051460
Issue Date:
DOI: https://doi.org/10.1007/BF00051460