Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway ROLE OF PALMITIC ACID

Abstract Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here, we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared to mono-cultured melanoma. Besides, fluorescently labeled fatty acid BODIPY FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provides fatty acids to melanoma cells. Compared to mono-cultured melanoma, co-cultured melanoma cells had higher proliferation and phospho-Akt (Ser473 and Thr450) expression. Overexpression of Akt mutants in melanoma cells reduced the coculture-enhanced proliferation. Lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation; changed the cell cycle distribution and increased phospho-Akt (Ser473 and Thr450), PI3K, but not phospho-PTEN expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells; and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significant larger tumor in mice compared to control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid which promotes melanoma cell growth by activating Akt.