Skip to main content
Log in

Matrix degrading metalloproteinases

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

Matrix degrading metalloproteinases are enzymes that degrade proteins in tissue extracellular matrices. These proteinases exhibit specific, well defined properties that allow them to be classified into a family of enzymes. They are secreted by various cell types as the cells effect their surrounding extracellular matrix. Such effects occur during normal physiologic tissue remodeling but also during pathologic processes such as tumor cell invasion and metastases. Currently there are seven proteases classified as members of the matrix metalloproteinase family and there are two putative members. Direct correlations can be made between the matrix metalloproteinases and normal tissue functions such as bone remodeling, uterine and mammary gland function and ovulation. The matrix metalloproteinases are also strongly associated with cancer progression in that they function to degrade epithelial basement membrane and stromal matrices in many different malignancies including brain tumors.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Nagase H, Barrett AJ, Woessner JF: Nomenclature and glossary of the matrix metalloproteinases. Matrix 1S: 421–424, 1992

    Google Scholar 

  2. Enzyme Nomenclature 1991. Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes, New York: Academic Press, 1992

  3. Nagase H, Ogata Y, Suzuki K, Enghild JJ, Salvesen G: Substrate specificies and activation mechanisms of matrix metalloproteinases. Biochem Soc Trans 19: 715–718, 1991

    Google Scholar 

  4. Senior RM, Griffin GL, Fliszar CJ, Shapiro SD, Goldberg GI, Welgus HG: Human 92- and 72-kilodalton type IV collagenases are elastases. J Biol Chem 266: 7870–7875, 1991

    Google Scholar 

  5. Matrisian LM: The matrix-degrading metalloproteinases. BioEssays 14: 455–463, 1992

    Google Scholar 

  6. Muller D, Quantin B, Gesnel MC, Millon-Collard R, Abecassis J: Breathnach R: The collagenase gene family in humans consists of at least four members. Biochem J 253: 187–192, 1988

    Google Scholar 

  7. Welgus HG, Fliszar CJ, Seltzer JL, Schmid TM, Jeffrey JJ: Differential susceptibility of type X collagen to cleavage by two mammalian interstitial collagenases and 72-kDa type IV collagenase. J Biol Chem 265: 13521–13527, 1990

    Google Scholar 

  8. Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, Podhajcer OL, Chenard MP, Rio MC, Chambon P: A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348: 699–704, 1990

    Google Scholar 

  9. Shapiro SD, Griffen GL, Gilbert DJ, Jenkins NA, Copeland NG, Welgus HG, Senior RM, Ley TJ: Molecular cloning, chromosomal location and bacterial expression of a novel murine macrophage metalloelastase. J Biol Chem 267: 4664–4671, 1992

    Google Scholar 

  10. Liotta LA, Steeg PS, Stetler-Stevenson WG: Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64: 327–336, 1991

    Google Scholar 

  11. Matrisian LM: Metalloproteinases and their inhibitors in matrix remodeling. TIG 6: 121–125, 1990

    Google Scholar 

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

    Google Scholar 

  13. Boone TC, Johnson ME, De Clerk YA, Langley KE: cDNA cloning and expression of a metalloproteinase inhibitor related to tissue inhibitor of metalloproteinases. Proc Natl Acad Sci USA 87: 2800–2804, 1990

    Google Scholar 

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

    Google Scholar 

  15. Khokha R, Waterhouse P, Yagel S, Lala PK, Overall CM, Norton G, Denhardt DT: Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells. Science 244: 947–950, 1989

    Google Scholar 

  16. De Clerk YA, Yenn T-D, Ratzkin BJ, Lu HS, Langley KE: Purification and characterization of two related but distinct metalloproteinase inhibitors secreted by bovine aortic endothelial cells. J Biol Chem 264: 17445–17453, 1989

    Google Scholar 

  17. DeClerk YA, Yean T-D, Lu HS, Ting J, Langley KE: Inhibition of autoproteolytic activation of interstitial procollagenase by recombinant metalloproteinase inhibitor MI/TIMP-2. J Biol Chem 266: 3893–3899, 1991

    Google Scholar 

  18. Brown CC, Hembry RM, Reynolds JJ: Immunolocalization of metalloproteinases and their inhibitor in the rabbit growth plate. J of Bone and Joint Surg 71: 580–593, 1989

    Google Scholar 

  19. DenBesten PK, Heffernan LM, Treadwell BV, Awbrey BJ: The presence and possible functions of the matrix metallo-proteinase collagenase activator protein in developing enamel matrix. Biochem J 264: 917–920, 1989

    Google Scholar 

  20. Southgate KM, Davies M, Booth RFG, Newby AC: Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation. Biochem J 288: 93–99, 1992

    Google Scholar 

  21. Curry TEJr, Mann JS, Estes RS, Jones PBC: alpha2-Macroglobulin and tissue inhibitor of metalloproteinases: collagenase inhibitors in human preovulatory ovaries. Endocrinology 127: 63–68, 1990

    Google Scholar 

  22. Librach CL, Werb Z, Fitzgerald ML, Chiu K, Corwin NM, Esteves RA, Grobelny D, Galardy R, Damsky CH, Fisher SJ: 92-kD Type IV collagenase mediates invasion of human cytotrophoblasts. J Cell Biol 113: 437–449, 1991

    Google Scholar 

  23. Graham CH, Lala PK: Mechanism of control of trophoblast invasion in situ. J Cell Physiol 148: 228–234, 1991

    Google Scholar 

  24. Woessner JF, Taplin C: Purification and properties of a small latent matrix metalloproteinase of the rat uterus. J Biol Chem 263: 16918–16925, 1988

    Google Scholar 

  25. Martelli M, Campana A, Bischof P: Secretion of matrix metalloproteinases by human endometrial cellsin vitro. J Reprod Fertil 98: 67–76, 1993

    Google Scholar 

  26. Talhouk RS, Chin JR, Unemori EN, Werb Z, Bissell MJ: Proteinases of the mammary gland: developmental regulationin vivo and vectorial secretion in culture. Development 112: 439–149, 1991

    Google Scholar 

  27. Lefebvre O, Wolf C, Limacher J-M, Hutin P, Wendling C, LeMeur M, Basset P, Rio M-C: The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J Cell Biol 119: 997–1002, 1992

    Google Scholar 

  28. Liotta LA, Stetler-Stevenson WG: Tumor invasion and metastasis: An imbalance of positive and negative regulation. Cancer Res 51 Suppl: 5054s-5059s, 1991

    Google Scholar 

  29. Matrisian LM, Bowden GT, Krieg P, Furstenberger G, Briand J-P, Leroy P, Breathnach R: 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, 1986

    Google Scholar 

  30. Rao JS, Steck PA, Mohanam S, Stetler-Stevenson WG, Liotta LA, Sawaya R: Elevated levels ofM r 92, 000 type IV collagenase in human brain tumors. Cancer Res 53: 2208–2211, 1993

    Google Scholar 

  31. Colton CA, Keri JE, Chen W-T, Monsky WL: Protease production by cultured microglia: Substrate gel analysis and immobilized matrix degradation. J Neurosci Res 35: 297–304, 1993

    Google Scholar 

  32. Nakano A, Tani E, Miyazaki K, Furuyama J, Matsumoto T: Expressions of matrilysin and stromelysin in human glioma cells. Biochem Biophys Res Commun 3: 999–1003, 1993

    Google Scholar 

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

    Google Scholar 

  34. Miyazaki K, Funahashi K, Numata Y, Koshikawa N, Akaogi K, Kikkawa Y, Yasumitsu H, Umeda M: Purification and characterization of a two-chain form of tissue inhibitor of metalloproteinases (TIMP) type 2 and a low molecular weight TIMP-like protein. J Biol Chem 268: 14387–14393, 1993

    Google Scholar 

  35. Alexander CM, Werb Z: Targeted disruption of the tissue inhibitor of metalloproteinases gene increases the invasive behavior of primitive mesenchymal cells derived from embryonic stem cellsin vitro. J Cell Biol 118: 727–739, 1992

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ennis, B.W., Matrisian, L.M. Matrix degrading metalloproteinases. J Neuro-Oncol 18, 105–109 (1993). https://doi.org/10.1007/BF01050416

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01050416

Key words

Navigation