DUAL FUNCTION OF SPHINGOSINE-1-PHOSPHATE RECEPTOR 2 IN EPITHELIAL CELL MIGRATION

ROMERO, DJ; TARALLO, E; SANTACREU, BJ; CHAVEZ FLORES, JC; PESCIO, LG; FAVALE, NO

Paraná

Congreso; 54th Annual Meeting Argentine Society for Biochemistry and Molceular Biology; 2018

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Epithelial cell differentiation is a process that involves the mesenchymal to epithelium transition (MET) and includes cell cycle arrest, cell-cell junction maturation in addition to changes in cell migration capacity. Previous results from our laboratory showed that Madin-Darby Canine Kidney (MDCK) cultured in hypertonic medium activate a cell differentiation program that depends on changes in sphingolipid metabolism. One of the most important sphingolipids is sphingosine-1-phosphate (S1P) that can act both intracellularly as second messenger and extracellularly as ligand for cell surface receptors (S1PRs). In the present work we evaluated the importance of S1P in the modulation of cell migration and its association with cell differentiation. We performed wound healing, colony dispersal and immunofluorescence studies using proliferative, polarized and differentiated MDCK cells. S1P receptor 2 (S1PR2) inhibition mediated by the specific antagonist JTE-013 increased the migration capacity of polarized and proliferative cells, while the opposite effect was found in differentiated cells. In colony dispersal assays, proliferative cells overexpressing S1PR2 failed to migrate and formed tightly clustered colonies. These results suggest that S1PR2 plays a dual role, acting both as a migration inhibitor and promoter depending on the differentiation stage of epithelial cells.