MOLECULAR REGULATION OF CELLULAR INVASION - ROLE OF GELATINASE-A AND TIMP-2

Extracellular matrix (ECM) turnover is an event that is tightly regula ted. Much of the coordinate (physiological) or discoordinate (patholog ical) degradation of the ECM is catalyzed by a class of proteases know n as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usual ly secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators a nd inhibitors. One member of the matrixin family, gelatinase A, is reg ulated differently from other MMPs, suggesting that it may play a uniq ue role in cell-matrix interactions, including cell invasion. The conv ersion from the 72 kDa progelatinase A to the active 62 kDa species ma y be a key event in the acquisition of invasive potential. This discus sion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue i nhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane con taining metalloproteinases (MT-MMP) in this process.