Membrane associated matrix metalloproteinases in metastasis

Hematogenous metastasis is postulated to involve tumor cell-initiated degradation of basement membrane barriers and underlying connective tissue matrices. Matrix metalloproteinases (MMP) are zinc-dependent endopeptidases that have been implicated in the proteolytic events of tumor cell invasion. Research has revealed a class of membrane-anchored metalloproteinases (MT-MMPs) and has provided convincing evidence that these enzymes activate latent MMP-2 (72 kDa gelatinase A) on the cell surface. The activation of plasma membrane associated MMP is a potential mechanism for facilitation of cellular metastasis and requires consideration when addressing potential roles of MMPs in tumor progression. This review focuses on potential in vivo regulatory mechanisms of membrane-associated MMP activity in the context of tumor cell interaction with matrix macromolecules. BioEssays 1999;21:940-949.