Abstract

Abstract We hypothesized that obesity cause inflammation which, in turn, promotes colon carcinogenesis. To test the hypothesis mouse intestinal IEC-6 cells were incubated in the presence of pre-conditioned media collected from culturing LPS-stimulated macrophage, followed by comparing protein expression profile with control cells. Our proteomic study revealed 45 differentially regulated proteins in mouse intestinal IEC-6 cells under state of inflammation. Among others, galectin-3, a beta-galactoside-binding protein, was up-regulated. Galectin-3 has been reported to play anti-apoptotic role in tumor progression and metastasis, and its over-expression has been observed in several types of cancer such as colon cancer. In order to determine relationship between obesity-induced inflammation and colon carcinogenesis, conditioned media (CM) from LPS-stimulated 3T3-L1 pre-adipocytes or differentiated adipocytes were utilized to culture IEC-6 cells. The CM was analyzed for levels of nitric oxide (NO), TNF-α and IL-6, and IEC lysates were analyzed for galectin-3 expression by western blot. Results showed that enhanced generation of NO, TNF-α and IL-6 resulted in upregulation of galectin-3 with respect to incubation time. Also, cytokine concentration was correlated to level of galectin-3, as verified by incubating IEC with increasing concentration of TNF-α or IL-6. These results indicate involvement of pro-inflammatory mediators from pre-adipocytes and adipocytes in colon carcinogenesis, in which galectin-3 may play a crucial role. 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 4579.

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