Résumé
PAI-1 is a SERPIN found either soluble or bound to vitronectin in the matrix. In both cases, PAI-1 is a fast acting inhibitor for uPA. By that mean PAI-1 modulates all the processes influenced by uPA, such as development, wound healing, cancer cell migration, proteolysis, and in general, cell matrix interactions. In cell adhesion, PAI-1 plays directly a contradictory role: 1. interfering in Vitronectin/Integrin linking, i.e. in de adhesion, 2. as a member of the tripartite complex uPAR/uPA/PAI-1, promotes the linking of the cell membrane to ECM, i.e. intermediate adhesion. PAI-1 has also been evoked in another key cell function, migration and we previously showed that cancer cells of high invasivity were parallely increasing their migration when surrounded by a PAI-1 coat (1). As such, PAI-1 already appeared as an extracellular modulator of cell function. Here we present several additional experimental arguments for considering PAI-1 as a novel member of the matricellular protein family (2). 1. In an in vitro epithelial cell wound-healing model, where the main process is cell migration, a) we have shown that antibodies directed against PAI-1 were able to decrease the rate of closure; b) PAI-1 was expressed as an ECM-bound protein within 6 hours after wounding. 2. In epithelial colon cancer cells, a) matrix PAI-1 was able to reorganize the actin cytoskeleton (producing actin rings) and lead to the modification of the Rho/Rock pathway; b) matrix PAI-1 induces cell blebbing and amaeboid migration, a strong modification of cell behaviour. 3. In invasive mammary cancer cells, a) the expression of PAI-1 mRNAs was correlated with the presence of the transcription factor SNAIL, a major pro-migratory factor involved in embryogenesis, and cancer invasion; b) matrix PAI-1 induced an increase in steady state PAI-1 mRNA levels in cells where the expression of SNAIL has been switched off. These data strongly suggest matrix PAI-1 as an extracellular modulator of cell function, referring to the main family of matricellular protein.