Proteolysis directed by the extracellular matrix

The degradation of extracellular matrix (ECM) during physio-pathological processes involves, essentially, two proteolytic systems: the plasmin (ogen) system and the matrix metalloproteinase (MMP) family. Enzyme activity necessitates the formation of proteolytic cascades acting in the pericellular environment. Several proteins (proteases, integrins, matrix, inhibitors, activators...) participate to enzyme catalysis forming assemblies within specialized plasma membrane structures (invadopodia, caveolae). MMP-mediated ECM degradation leads to the formation of peptides (matricryptins, matrikins) which, in turn, can modulate MMP expression. MMPs (especially gelatinases) can also activate growth factors as pro TGF beta or liberate those factors from matrix sites. Interaction between matrix and gelatinases was shown to influence enzyme activation through several mechanisms. Finally, thrombospondins 1 and 2, matricellular proteins, can regulate gelatinase A by favoring its endocytosis. Those data emphasize the potential interest of certain matrikins or pseudo-matrikins as therapeutic agents to control cell invasion.