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Role of the extracellular matrix in the degradation of connective tissue

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Abstract

Cell-matrix interactions have an important impact on regulating connective tissue degradation during physiological and pathological processes, e.g., development, wound healing and tissue remodeling and tumor invasion and metastasis. Connective tissue breakdown is initiated by a specific class of enzymes, the matrix metalloproteinases, which include the type I collagenases, the type IV collagenases/gelatinases and the stromelysins and which vary with respect to their substrate specificities. The activity of the metalloproteinases is regulated by de novo synthesis of the proenzymes, the activation of the zymogens and by the presence of the inhibitors, TIMPs. This tight control is required in order to guarantee normal functioning of connective tissue.

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References

  1. Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T (1992) Proteolytic processing of the 72,000 Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res 202: 471–476

    Google Scholar 

  2. Eeckhout Y, Vaes G (1977) Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Biochem J 166: 21–31

    Google Scholar 

  3. Docherty AJP, O'Connell J, Crabbe T, Angal S, Murphy G (1992) The matrix metalloproteinases and their natural inhibitors: prospects for treating degenerative tissue diseases. Trends Biotechnol 10: 200–207

    Google Scholar 

  4. Birkedal-Hansen H, Moore WGI, Bodden MK, Windsor LJ, Birkedal-Hansen B, et al (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4: 197–250

    Google Scholar 

  5. Woessner JF Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5: 2145–2154

    Google Scholar 

  6. Fessler L, Duncan K, Fessler JH, Salo T, Tryggvason K (1984) Characterization of the procollagen IV cleavage products produced by a specific tumor collagenase. J Biol Chem 259: 9783–9789

    Google Scholar 

  7. Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P et al (1990) A new member of the metalloproteinase gene family is specifically expressed in stromal but not in tumor cells of breast carcinomas. Nature 348: 699–704

    Google Scholar 

  8. Goldberg GI, Marmer BL, Grant GA, Eisen AZ, Wilhelm S et al (1989) Human 72 kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteinases designated TIMP-2. Proc Natl Acad Sci USA 86: 8207–8211

    Google Scholar 

  9. Stetler-Stevenson WG, Krutzsch HC, Liotta LA (1989) Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family. J Biol Chem 264: 17374–17378

    Google Scholar 

  10. Howard EW, Bullen EC, Banda MJ (1991) Regulation of the autoactivation of human 72 kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem 266: 13064–13069

    Google Scholar 

  11. MacNaul KL, Chartrain N, Lark M, Tocci MJ, Hutchinson NI (1990) Discoordinate expression of stromelysin, collagenase and tissue inhibitor of metalloproteinase-1 in rheumatoid human synovial fibroblasts. Synergistic effects of interleukin-1 and tumor necrosis factor-α on stromelysin expression. J Biol Chem 265: 17238–17245

    Google Scholar 

  12. Unemori EN, Bair MJ, Bauer EA, Amento EP (1991) Stromelysin expression regulates collagenase activation in human fibroblasts. J Biol Chem 266: 23477–23482

    Google Scholar 

  13. Salo T, Lyons JG, Rahemtulla F, Birkedal-Hansen H, Larjava H (1991) Transforming growth factor-Β1 upregulates type IV collagenase expression in cultured human keratinocytes. J Biol Chem 266: 11436–11441

    Google Scholar 

  14. Overall CM, Wrana JL, Sodek J (1991) Transcriptional and post-transcriptional regulation of 72 kDa gelatinase/type IV collagenase by transforming growth factor-Β1 in human skin fibroblasts. J Biol Chem 266: 14064–14071

    Google Scholar 

  15. Peppin GJ, Weiss SJ (1986) Activation of endogenous metalloproteinase, gelatinase, by triggered human neutrophils. Proc Natl Acad Sci USA 83: 4322–4326

    Google Scholar 

  16. Angel P, Baumann I, Stein B, Delius H, Rahmsdorf HJ et al (1987) 12-O-Tetradecanoyl-phorbol-13-acetate-induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region. Mol Cell Biol 7: 2256–2266

    Google Scholar 

  17. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ et al. (1987) Phorbolester-inducible genes contain a common cis element recognized by TPA-modulated trans-acting factor. Cell 49: 729–739

    Google Scholar 

  18. Kerr LD, Holt JT, Matrisian LM (1988) Growth factors regulate transin gene expression by c-fos-dependent and c-fos-independent pathways. Science 242-1424-1427

  19. Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja J et al (1991) Complete structure of the human gene for 92 kDa type IV collagenase. Divergent regulation of expression for the 92 and 72 kilodalton enzyme genes in HT-1080 cells. J Biol Chem 266: 16485–16490

    Google Scholar 

  20. Auble DT, Brinckerhoff CE (1991) The AP-1 sequence is necessary but not sufficient for phorbol induction of collagenase in fibroblasts. Biochemistry 30: 4629–4635

    Google Scholar 

  21. Gutman A, Wasylyk B (1990) The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J 9: 2241–2246

    Google Scholar 

  22. Buttice G, Quinones S, Krukinen M (1991) The AP-1 site is required for basal expression but is not necessary for TPA-response of the human stromelysin gene. Nucl Acids Res 19: 3723–3731

    Google Scholar 

  23. Howard EW, Bullen EC, Banda MJ (1991) Preferential inhibition of 72 and 92 kDa gelatinases by tissue inhibitor of metalloproteinases-2. J Biol Chem 266: 13070–13075

    Google Scholar 

  24. Liotta LA, Rao CN, Wewer UM (1986) Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem 55: 1037–1057

    Google Scholar 

  25. Chiquet-Ehrisman R, Mackie EJ, Pearson CA, Sakakura T (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47: 131–139

    Google Scholar 

  26. Ruoslathi E (1991) Integrins. J Clin Invest 87: 1–5

    Google Scholar 

  27. Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48: 549–554

    Google Scholar 

  28. Buck CA, Horwitz AF (1987) Cell surface receptors for extra-cellular matrix molecules. Annu Rev Cell Biol 3: 179–205

    Google Scholar 

  29. Otey CA, Pavalko FM, Burridge K (1990) An interaction between α-actinin and the Β1 integrin subunit in vitro. J Cell Biol 111: 721–729

    Google Scholar 

  30. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K (1986) Interaction of plasma membrane fibronectin receptor with talin, a transmembrane linkage. Nature 320: 531–533

    Google Scholar 

  31. Bell E, Ivarsson B, Merill C (1979) Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of differential proliferative potential in vitro. Proc Natl Acad Sci USA 76: 1274–1278

    Google Scholar 

  32. Tomasek JJ, Hay ED, Fujiwara K (1982) Collagen modulates cell shape and cytoskeleton of embryonic cornea and fibroma fibroblasts: distribution of actin, α-actinin and myosin. Dev Biol 92: 107–122

    Google Scholar 

  33. Mauch C, Hatamochi A, Scharffetter K, Krieg T (1986) Regulation of collagen synthesis within a three-dimensional collagen gel. Exp Cell Res 178: 493–503

    Google Scholar 

  34. Mauch C, Adelmann-Grill BC, Hatamochi A, Krieg T (1989) Collagenase gene expression in fibroblasts is regulated by a three-dimensional contact with collagen. FEBS Lett 250: 301–305

    Google Scholar 

  35. Klein CE, Dressel D, Steinmayer T, Mauch C, Eckes B et al (1991) Integrin α2Β1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorsanization of collagen I fibrils. J Cell Biol 115: 1427–1436

    Google Scholar 

  36. Schiro JA, Chan BM, Roswit WT, Kassner PD, Pentland AP et al (1991) Integrin α2Β1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell 67: 403–410

    Google Scholar 

  37. Kornberg LJ, Earp HS, Turner CE, Prockop C, Juliano RL (1991) Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of Β1 integrins. Proc Natl Acad Sci USA 88: 8392–8396

    Google Scholar 

  38. Röckel D, Krieg T (1994) Three-dimensional contact with type I collagen mediates tyrosine phosphorylation in primary human skin fibroblasts. Exp Cell Res 211: 42–48

    Google Scholar 

  39. Werb Z, Tremble PM, Behrendtsen O, Crowley E, Damsky CH (1989) Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol 109: 877–889

    Google Scholar 

  40. Aggeler J, Frisch SM, Werb Z (1984) Changes in cell shape correlate with collagenase gene expression in rabbit synovial fibroblasts. J Cell Biol 98: 1662–1671

    Google Scholar 

  41. Unemori EN, Werb Z (1986) Reorganization of polymerized actin: a possible trigger in fibroblasts cultured in and on collagen gels. J Cell Biol 103: 1021–1031

    Google Scholar 

  42. Tryggvason K, HöythyÄ M, Salo T (1987) Proteolytic degradation of extracellular matrix in tumor invasion. Biochim Biophys Acta 907: 191–217

    Google Scholar 

  43. Stetler-Stevenson WG, Brown PD, Onisto M, Levy AT, Liotta LA (1990) Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J Biol Chem 265: 13933–13938

    Google Scholar 

  44. Garbissa S, Scagliotti G, Masiero L, DiFrancesco C, Caenazzo C et al (1992) Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy. Cancer Res 52: 4548–4549

    Google Scholar 

  45. Sato H, Kida Y, Mai M, Endo Y, Sasaki T et al (1992) Expression of genes encoding type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells. Oncogene 7: 77–83

    Google Scholar 

  46. Matrisian LM, Bowden GT, Krieg P, Fürstenberger G, Briand P et al (1986) The mRNA coding for the secreted protease transin is expressed more abundantly in malignant than in benign tumors. Proc Natl Acad Sci USA 83: 9413–9417

    Google Scholar 

  47. Tryggvason K, HöythyÄ M, Pyke C (1993) Type IV collagenases in invasive tumors. Breast Cancer Res Treat 24: 209–218

    Google Scholar 

  48. Pyke C, Ralfkiaer E, Huhtala P, Hurskainen T, DanØ K et al (1992) Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. Cancer Res 52: 1336–1341

    Google Scholar 

  49. Poulsom R, Hanby AM, Pignatelli M, Jeffrey RE, Longcroft JM et al (1993) Expression of gelatinase A and TIMP-2 mRNAs in desmoplastic fibroblasts in both mammary carcinomas and basal cell carcinomas of the skin. J Clin Pathol 46: 429–436

    Google Scholar 

  50. Poulsom R, Pignatelli M, Stetler-Stevenson WG, Liotta LA, Wright PA et al (1992) Stromal expression of 72 kDa type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. Am J Pathol 141: 389–396

    Google Scholar 

  51. Autio-Harmainen H, Karttunen T, Hurskainen T, HöyhtyÄ M, Kauppila A et al (1993) Expression of 72 kDa type IV collagenase (gelatinase A) in benign and malignant ovarian tumors. Lab Invest 69: 312–321

    Google Scholar 

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

    Google Scholar 

  53. Polette M, Clavel C, Muller D, Abecassis J, Binninger I et al (1991) Detection of mRNAs encoding collagenase I and stromelysin-2 in carcinomas of the head and neck by in situ hybridization. Invasion Metastasis 11: 76–83

    Google Scholar 

  54. Wolf C, Chemnard M-P, de Grossouvre P, Bellocq J-P, Chambon P et al (1992) Breast cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing. J Invest Dermatol 99: 870–872

    Google Scholar 

  55. Muller D, Wolf C, Abecassis J, Millon R, Engelmann A et al (1993) Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res 53: 165–169

    Google Scholar 

  56. Bauer EA, Uitto J, Walters RC, Eisen AZ (1979) Enhanced collagenase production by fibroblasts derived from human basal cell carcinomas. Cancer Res 39: 4594–4599

    Google Scholar 

  57. Hernandez AD, Hibbs MS, Postlethwaite AE (1985) Establishment of basal cell carcinoma in culture: evidence for a basal cell carcinoma-derived factor(s) which stimulates fibroblasts to proliferate and release collagenase. J Invest Dermatol 85: 470–475

    Google Scholar 

  58. Kataoka H, DeCastro R, Zucker S, Biswas C (1993) Tumor cell-derived collagenase-stimulatory factor increases expression of intestitial collagenase, stromelysin, and 72-kda gelatinase. Cancer Res 53: 3154–3158

    Google Scholar 

  59. Goslen JB, Eisen AZ, Bauer EA (1985) Stimulation of skin fibroblast collagenase production by a cytokine derived from basal cell carcinomas. J Invest Dermatol 85: 161–164

    Google Scholar 

  60. Biswas C (1982) Tumor cell stimulation of collagenase production by fibroblasts. Biochem Biophys Res Commun 109: 1026–1034

    Google Scholar 

  61. Biswas C, Nugent MA (1987) Membrane association of collagenase stimulatory factor(s) from B-16 melanoma cells. J Cell Biochem 35: 247–258

    Google Scholar 

  62. Ellis SM, Nabeshima K, Biswas C (1989) Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor. Cancer Res 49: 3385–3391

    Google Scholar 

  63. Khokha R, Waterhouse P, Yagel S, Lala PK, Overall CM et al (1989) Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells. Science 243: 947–950

    Google Scholar 

  64. DeClerck YA, Yean T-D, Lu HS, Ting J, Langley KE (1992) Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 52: 701–708

    Google Scholar 

  65. Schultz RM, Silberman S, Persky B, Bajkowski AS, Carmichael DF (1988) Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion and lung colonization by murine B16-F10 melanoma cells. Cancer Res 48: 5539–5545

    Google Scholar 

  66. Ponton A, Coulombe B, Skup D (1991) Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity. Cancer Res 51: 2138–2143

    Google Scholar 

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  1. Klinik für Dermatologie und Venerologie der Universität zu Köln, Joseph-Stelzmannstrasse 9, D-50924, Köln, Germany

    C. Mauch & T. Krieg

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Mauch, C., Krieg, T. & Bauer, E.A. Role of the extracellular matrix in the degradation of connective tissue. Arch Dermatol Res 287, 107–114 (1994). https://doi.org/10.1007/BF00370728

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