Abstract 2283: The role of insulin-like growth factor-1 and insulin like growth factor-1 receptor in obesity and oesophageal cancer

Abstract

Abstract Introduction: The insulin-like growth factor pathway, which is involved in cell proliferation, differentiation and protection against apoptosis, has been implicated in esophageal cancer progression. This study examined the role of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) as a potential mechanism linking obesity with esophageal cancer. Methods: IGF-1R expression in esophageal squamous cell carcinoma (KYSE, OE21) and adenocarcinoma (OE19, OE33) cell lines was measured by Western analysis and the effect of IGF-1 (0.1 − 1000 ng/ml) on survival of cell lines in relation to their expression of IGF-1R was assessed by MTT assay. Circulating levels of IGF-I were measured in 50 human serum samples by ELISA and immunohistochemistry determined IGF-1R expression in human tumor sections. Results were related to tumor type, BMI and survival. Results: Higher IGF-1R expression was observed in squamous cell carcinoma cell lines, however only adenocarcinoma cell lines showed significantly increased cell survival in response to IGF-1 (p <0.001). Significantly higher circulating levels of IGF-1 were observed in patients with adenocarcinoma (p = 0.02). In resected esophageal tumor sections, no statistical difference between intensity of IGF-1R expression and BMI or survival was observed, however reduced survival was observed in patients with moderate-strong compared to weak-negative IGF-1R expression. Higher intensity IGF-1R staining was observed in the ‘immune cell rich’ leading edge of adenocarcinomas. Conclusion: This study suggests an important role for IGF-1 in esophageal adenocarcinoma cell survival. Novel findings relating to high IGF-1R expression in the leading edge of esophageal adenocarcinoma and possible associations with obesity are also presented. 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 2283.