CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Alpha 2 Macroglobulin/LRP1 system induces cell migration and proliferation by intracellular signaling activation
Autor/es:
FERRER D; CACERES LC; JALDIN-FINCATI JR; SÁNCHEZ MC; CHIABRANDO GA
Lugar:
Puerto Madryn
Reunión:
Congreso; XLVI Annual Meeting - Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2010
Resumen:
Alpha2-Macroglobulin (a2M) is a broad specific proteinase inhibitor, which is recognized by LDL receptor-related protein 1 (LRP1), an endocytic receptor belonging to the LDL receptor gene family. Previously, we demonstrated that a2M/LRP1 system induces intracellular signaling activation characterized by the activation of PKC α/β, MAPK-ERK1/2 and NFkB, which downstream mediated the MMP-9 expression in macrophage-derived cell lines. It is know that these intracellular signaling pathways are involved in cell migration and proliferation. Thus, in this work we investigated whether a2M/LRP1 system is mediating these cellular events using different cell lines (RAW 264.7 and HT-1080). By wound-healing assays we observed that α2M increased the cellular motility of RAW 264.7 cells. In addition, by BrdU ((5-bromo-2-deoxyuridine) and flow cytometry we show that α2M induced cellular proliferation of HT-1080 cells. Both cellular events were fully blocked by pharmacological inhibitors of PKC α/β, MAPK-ERK1/2 and NFkB (GÖ-6976, PD98059 and BAY) as well as by negative dominant mutants of intracellular signaling intermediates such as RAS N17 and MEK AA. In conclusion, our data demonstrate that α2M/LRP1 system promotes the cell migration and proliferation by downstream activation of multiple intracellular signaling pathways.