Colon cancer is the third most common cause of cancer, and epidemiological studies have shown that obesity increases the risk of colon cancer by 1.5-2 folds with obesity-associated colon cancer accounting for 14- 35% of total incidence. So far, solely leptin was found to promote the motility and invasion of carcinoma cells. Adiponectin is another prominent protein hormone secreted by differentiated adipocytes. However, the effect of adiponectin on migration of carcinoma cells is mostly unknown. In this study, we found that adiponectin significantly increased the locomotion of human SW480 colon carcinoma cells. This pro-migratory effect is mediated by an activation of an autocrine loop of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), as was shown by neutralizing antibodies. Treatment of the cells with these specific antibodies completely abrogated the adiponectin-promoted locomotion. The intracellular signal transduction underlying this effect involves the activity of the transcription factors Stat-3 and nuclear factor-kappa B (NFκB), but also the activation of the phosphatidylinositol- 3-kinase/Akt pathway, as proven by the use of specific inhibitors. Blockade of NFκB activation abolished the pro-migratory effect of adiponectin by inhibiting the secretion of IL-8 and MCP-1. Here, we report on a new biological function of adiponectin in the regulation of colon cancer progression by stimulating tumor cell migration via an autocrine IL-8 and MCP-1 loop. Thus our findings have potential clinical implications, because understanding the impact of adiponectin on tumor cell migration and the underlying signal transduction mechanisms is mandatory for future development of novel therapeutics to treat obesity-associated colorectal cancer.
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