[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.
Hornebeck
William
W
FRE 2534 CNRS-IFR 53 Biomolécules, Faculté de Médecine, 51 rue Cognacq Jay, 51095 Reims, France. william.hornebeck@univ-reims.fr
Emonard
Hervé
H
Maquart
François-Xavier
FX
Bellon
Georges
G
D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D005353:Fibronectins; D006133:Growth Substances; D010455:Peptides; D016212:Transforming Growth Factor beta; D010450:Endopeptidases; D005341:Fibrinolysin; D020782:Matrix Metalloproteinases