EXPRESSION OF TUMOR NECROSIS FACTOR ALPHA nRECEPTOR I MODULATES MELANOMA CELL MIGRATION

SANCHEZ ES; RODRIGUEZ Y; CAMPOS L; BLANCO H; ELICABE J; DI GENARO MS; ALVAREZ SE

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Melanoma progression is suggested to depend on specific factors of the inflammatory microenvironment. When produced in this microenvironment, tumor necrosis factor alpha (TNF) promotes cancer. TNF signals through the p55 receptor (TNFRI) to activate nuclear factor-kappa B (NF-kB). Precisely, NF-kB has been pointed as a link between cancer and inflammation, which prompted us to investigate how the expression of TNFRI affects melanoma progression with special emphasis on NF-kB induction. To this end, we isolated peritoneal macrophages from wild type and TNFRI-/- mice. Cells were stimulated with LPS and conditioned media (CM) was collected. By ELISA, we determined that interleukin (IL) 1, IL6, IL12, TNF and NO levels were higher in TNFRI-/- CM. The CM was used as a chemo attractant to evaluate migration of B16 melanoma cells in a modified Boyden Chamber. Interestingly, while CM obtained from wt macrophages inhibits migration, TNFRI-/- CM increases it. Thus, we suggest that an enhanced inflamed microenvironment in TNFRI-/- mice supports melanoma progression. Moreover, while we have previously shown that sphingosine-1-phosphate (S1P) is a bioactive lipid required for TNF-induced NF-kB activation, our new preliminary data indicate that a differential expression of S1P receptors in melanoma cells may also regulate its invasive capability. Funded by Florencio Fiorini Foundation.