Abstract 1104: Insulin-like growth factor-1 is elevated in viscerally obese oesophageal adenocarcinoma patients and expression of its receptor correlates with tumor invasiveness

Abstract

Abstract The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer development. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and squamous cell carcinoma (SCC) progression. IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE410, OE21) and adenocarcinoma (OE19, OE33) cell lines by Western Blotting. Tumor cell proliferation in response to IGF-1 was assessed by BrdU incorporation assay. Circulating levels of IGF-1 were measured in 99 serum samples by ELISA and IGF-1R expression was assessed in 50 resected tumor specimens by immunohistochemistry. Results were related to tumor type, gender and visceral adiposity. Higher IGF-1R mRNA and protein expression were observed in SCC cells, however only adenocarcinoma cell lines showed significantly increased cell proliferation in response to IGF-1 (p<0.01). Significantly higher circulating levels of IGF-1 were detected in patients who had adenocarcinoma (p<0.05) and who were viscerally obese (p<0.05). In resected esophageal adenocarcinoma, IGF-1R expression significantly increased as the tissue progressed along the malignant sequence, with the highest expression observed at the invasive leading edge of the tumor. Uniform IGF-1R expression was observed in SCC tumors. This novel study is the first of its kind to examine both the differential role of the IGF system in esophageal adenocarcinoma and SCC, and also its association with visceral obesity. These data indicate that in esophageal adenocarcinoma, the IGF-1 axis plays a key role in malignant progression and represents a plausible mechanism by which visceral obesity increases esophageal adenocarcinoma risk. 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 1104. doi:10.1158/1538-7445.AM2011-1104