Abstract 970: Obesity promotes melanoma metastasis by modulating Snai1 and KiSS1 expression

Abstract

Abstract Malignant melanoma accounts for 75% of deaths associated with skin cancer. Its lethality comes from its aggressive metastasis to secondary sites such as the lungs. Epidemiological and animal studies suggest that obesity may increase the ability of melanomas to metastasize. The objective of these studies was to determine the mechanism by which obesity increases the aggressiveness of melanomas to metastasize. To this end, we used ob/ob mice as a model of obesity, as well as different cell culture conditions which mimic obesity, to investigate the molecular mechanism by which obesity affects the metastatic phenotype of B16BL6 mouse metastatic melanoma cells in vitro. In cell culture, we showed that serum from obese mice increased the ability of melanoma cells to invade. We showed that both obese mouse serum and conditioned medium collected from mature 3T3L1 adipocytes promoted a mesenchymal phenotype, as seen by an increased expression of genes associated with this phenotype, such as Snai1, and a corresponding decreased expression of the metastasis suppressor gene KiSS1. Our preliminary results suggest that obesity may increase the metastatic ability of melanomas via the pro-inflammatory cytokine Interleukin 6 (IL-6). Therefore, our hypothesis is that obesity promotes melanoma metastasis by promoting the epithelial-to-mesenchymal transition (EMT) and its associated phenotypic changes by up-regulating Snai1 and down-regulating KiSS1 through IL-6. These findings will help us understand how obesity affects melanoma metastasis and allow us to identify key cellular signaling pathways that can be used to prevent or possibly inhibit melanoma metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 970. doi:10.1158/1538-7445.AM2011-970