MATRIX METALLOPROTEINASES AND INVASION BY CANCER CELLS Matrix metalloproteinases (MMP) also called matrixin belong to the family of metalloendopeptidases. This family includes matrixin, thermolysin, astacin, serratia and snake venom metalloproteinases. Within the matrixin family, at least three distinct subsets of enzymes which include collagenases, gelatinases and stromelysins with at least nine protein members have been recognized (table I). These enzymes possess the ability to degrade extracellular matrix components including collagens, gelatins, fibronectin, laminin and proteoglcan. Table I. The matrix metalloproteinase (matrixin) family _______________________________________________________ Group MMP# Other names assigned _______________________________________________________ Collagenases MMP-1 Interstitial collagenase, CLG, CLGN EC 3.4.24.7 MMP-8 PMN collagenase, CLG1 EC 3.4.24.34 Gelatinases MMP-2 Gelatinase A 72 kD gelatinase Type IV collagenase EC 3.4.24.24 MMP-9 Gleatinase B 92 kD gelatinase Type IV collagenase EC 3.4.24.35 MMP-7 Punctuated MP (PUMP) Matrilysin Uterine MP EC 3.4.24.23 Stromelysins MMP-3 Stromelysin-1 Transin (rat) Procollagenase activator EC 3.4.24.17 MMP-10 Stromelysin-2 Transin-2 (rat) EC 3.4.24.22 MMP-11 Stromelysin-3 Others MMP-12 Metallo-elastase (mouse) MMP-13 COLLAGENASE 3; CLG3 MMP-14 MMP14, MEMBRANE-TYPE _______________________________________________________ Adapted from S Tabibzadeh, The signals and molecular pathways involved in human mentruation, a unique process of tissue destruction and remodelling. Mol Hum Reprod 2, 77-92, 1996 In the May 31, 96 issue of Cell, Brooks et al, described that one of the members of the metalloportease family, MMP-2, was expressed on the surface of the cancer cells including melanoma cells in vitro. They also demonstrated that this molecule bound to integrin v3. Both MMP-2 and v3 were found on the angiogenic blood vessels and melanoma cells in vivo. Presence of MMP-2 on the surface of tumor cells not only aids the degradation of extracellular matrix by the neoplastic cells, it facilitates their motility and directed cell invarion. Peter C. Brooks, Staffan Strömblad, Luraynne C. Sanders, Tami L. von Schalscha, Ronald T. Aimes, William G. Stetler­Stevenson, James P. Quigley, and David A. Cheresh: Localization of Matrix Metalloproteinase MMP-2 to the Surface of Invasive Cells by Interaction with Integrin v3. Cell 1996