Abstract 5187: Migration and proliferation of colon carcinoma cells are importantly affected by leptin and adiponectin via diverse pathways

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Obesity is a dramatically increasing public health problem worldwide. Traditionally, fat tissue was considered to be solely an energy storage depot. However, recent studies have shown that adipose tissue exerts important endocrine functions, which are predominantly mediated by a network of various soluble factors derived from adipocytes. New evidence has come to light elucidating a modulatory role of this adipocytokines in the regulation of cancer development. The most prominent adipocytokines are leptin and adiponectin, which are predominantly secreted by differentiated adipocytes. Depending on the energy status of adipocytes, the secreted concentrations of leptin and adiponectin vary drastically. In obesity, serum level of leptin is considerable increased (greater than or equal to 100 nanogram/ml), whereas the adiponectin concentration is very low. In contrast, adiponectin concentration accelerates by weight reduction (greater than or equal to 10 microgram/ml). The aim of our study was to investigate the influence of adipocytokines on cancer cells. Using our three-dimensional, collagen-based migration assay we found a strong impact of leptin and adiponectin on the migration of colon cancer cells. Both adipocytokines alone significantly enhanced the migratory activity of SW480 colon carcinoma cells from 30.3±7.4% spontaneously locomoting cells to 50.9±8.2%. In contrast, both adipocytokines in combination reduced the migration of colon carcinoma cells to control level. Moreover, treatment of the cells with leptin alone enhanced the proliferation of SW480 cells up to 50%, whereas adiponectin mediated an anti-proliferative function by 30%. Surprisingly, addition of leptin and adiponectin together did not have any effect on the proliferation. On the molecular level, leptin-induced migration was mediated by phosphorylation of focal adhesion kinase (FAK) and activation of phosphatidyl-inositol-3-kinase (PI3K). The pro-migratory effect of adiponectin was accompanied by an activation of PI3K/AKT and various transcription factors. In contrast, incubation with both adipocytokines in combination led to a decreased phosphorylation of FAK and AKT. Understanding the impact of leptin and adiponectin alone and their interplay on the carcinogenesis of colon cancer as well as the underlying molecular mechanisms have a major clinical significance, and provide the basis for the development of novel therapeutics to treat obesity-associated colorectal cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5187.