ALPHA-2M/LRP1 SYSTEM INDUCES CELL MIGRATION AND PROLIFERATION BY INTRACELLULAR SIGNALING ACTIVATION

FERRER DARIO; CACERES LEANDRO; JALDIN-FINCATI JAVIER; SANCHEZ MC; CHIABRANDO GUSTAVO

Puerto Madryn, Chubut

Congreso; XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Alpha2-Macroglobulin (alpha2M) 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 alpha2M/LRP1 system induces intracellular signaling activation characterized by the activation of PKC alpha/ß, MAPK-ERK1/2 and NFkB, which downstream mediated the MMP-9 expression in macrophagederived cell lines. It is know that these intracellular signaling pathways are involved in cell migration and proliferation. Thus, in this work we investigated whether alpha2M/LRP1 system is mediating these cellular events using different cell lines (RAW 264.7 and HT- 1080). By wound-healing assays we observed that alpha2M increased the cellular motility of RAW 264.7 cells. In addition, by BrdU (5-bromo-2-deoxyuridine) and flow cytometry we show that alpha2M induced cellular proliferation of HT-1080 cells. Both cellular events were fully blocked by pharmacological inhibitors of PKC alpha/ß, 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 alpha2M/LRP1 system promotes the cell migration and proliferation by downstream activation of multiple intracellular signaling pathways