SPHINGOSINE-1-PHOSPHATE INHIBITS MIGRATION OF HUMAN MELANOMA CELLS

CAMPOS L; CASTRO M; RODRIGUEZ Y; SANCHEZ ES; ALVAREZ SE

Mendoza

Congreso; XXXI Reunión Anual de la Sociedad de Biología de Cuyo; 2013

Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates many processes in cancer. S1P may act as an intracellular messenger or, after being transported outside the cell, in an autocrine/paracrine fashion to stimulate five G-protein coupled receptors, named S1P1-5. We have recently shown that intracellular S1P is required for NF-kB activation in melanoma, a deadly type of skin cancer. The majority of the mortality associated with different types of cancer involves migration and metastasis. Thus, we decided to study the role of S1P in migration of human melanoma cells. Since most of the melanoma patients display the BRAFV600E mutation, we used two cells lines in our study: SKMel2 (BRAF wild type) and Lu1205 (BRAFV600E). Migration was assessed by two methods: i) Boyden chamber and ii) scratch assay. SKMel2 cells do not migrate in our conditions. Remarkably, while fetal bovine serum (FBS) increases, S1P inhibits migration of Lu1205 cells in a dose dependent manner. Although it has been shown that S1P2 receptor prevents migration, by RT-PCR we determined that both cell lines express S1P1, S1P2 and S1P3 receptors. However, its relative levels are not established yet. Inhibition of migration is reverted by pre-incubation of cells with Bay 10-872, an NF-kB pathway inhibitor. Similar results were obtained in cell cultured in hypoxia, a hallmark of many cancers. Altogether, these results suggest that S1P is a negative regulator of melanoma migration in the tumor microenvironment.