Proteases associated with invadopodia, and their role in degradation of extracellular matrix

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 a 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.