Membrane associated matrix metalloproteinases in metastasis

Hematogenous metastasis is postulated to involve tumor cell-initiated degra dation of basement membrane barriers and underlying connective tissue matri ces. Matrix metalloproteinases (MMP) are zinc-dependent endopeptidases that have been implicated in the proteolytic events of tumor cell invasion. Res earch has revealed a class of membrane-anchored metalloproteinases (MT-MMPs ) and has provided convincing evidence that these enzymes activate latent M MP-2 (72 kDa gelatinase A) on the cell surface, The activation of plasma me mbrane associated MMP is a potential mechanism for facilitation of cellular metastasis and requires consideration when addressing potential roles of M MPs in tumor progression. This review focuses on potential in vivo regulato ry mechanisms of membrane-associated MMP activity in the context of tumor c ell interaction with matrix macromolecules. BioEssays 1999;21:940-949. (C) 1999 John Wiley & Sons, Inc.