Abstract

Metastasizing cancer cells invade the extracellular matrix using plasma membrane protrusions (invadopodia) that contact and dissolve the matrix. Evidence suggests that membrane-associated proteases, 170-kD gelatinase (seprase) and Gelatinase A, exert their mechanisms of action on invadopodia. Potential roles that other metallo- and serine-types of membrane proteases, including membrane-type matrix metalloprotease, meprin, dipeptidyl peptidase IV, fibroblast activation protein alpha and guanidinobenzoatase, play in the cell surface proteolysis are also discussed. It is proposed that formation of a structurally and functionally linked protease complex on invadopodia allows the invasion of cancer cells into the extracellular matrix.

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