Abstract 5185: Omental adipose tissue increases the proliferative, migratory and invasive capacity of esophageal adenocarcinoma via up regulation of focal adhesion and endothelial mesenchymal transition pathways
Authors: Allott Emma , Morine Melissa , Lysaght Joanne , Ravi Narayanasamy , Roche Helen , Reynolds John , Pidgeon Graham 
Published: February 2011

Introduction: The prevalence of obesity has increased markedly over the past two decades contributing to morbidity and mortality worldwide in the form of increasing rates of cardiovascular disease, diabetes and now cancer. Mirroring the exponential increase in obesity, the incidence of esophageal adenocarcinoma in Ireland has doubled over the last 15 years and obesity has been identified as an independent risk factor. Adipose tissue is now recognised as an important multifunctional endocrine organ with a range of biological activities in energy homeostasis as well as in the immune and inflammatory response, contributing to the state of low grade chronic inflammation often found in obese individuals. A detailed investigation of the molecular mechanisms linking obesity and cancer is required.

Method: Adipose tissue fragments, adipose conditioned media (ACM) and adipocytes were prepared from omental adipose tissue from matched viscerally obese esophageal adenocarcinoma patients (n=6) and their effect on gene expression in the esophageal adenocarcinoma OE33 cell line was examined by co-culture using Affymetrix arrays. Gene expression changes were validated in a larger cohort of esophageal adenocarcinoma (n=30) using quantitative RTPCR. Proliferation (BrdU cell proliferation ELISA), migration and invasion assays (Millipore) were used to assess the functional effect of these gene changes in esophageal adenocarcinoma cell lines (OE19, OE33).

Results: Following co-culture of esophageal adenocarcinoma with adipose tissue fragments and adipocytes, pathway analysis showed focal adhesion to be significantly enhanced via up regulation of SPP1, S100A8 and SEMA4B. Endothelial mesenchymal transition pathways were also significantly increased via up regulation of SNAI2/SLUG and laminin-5 while tumor suppressor CTDSPL was found to be down regulated by two fold. When esophageal adenocarcinoma cell lines (OE33, OE19) were cultured with ACM from omental adipose tissue, an increase in the proliferative, migratory and invasive phenotype of the tumor cells was observed.

Conclusion: Esophageal adenocarcinoma is an aggressive disease with poor five year survival and early lymphatic and haematogenous spread implying that pathways involved in tumor invasion and metastasis are of great significance. Obesity is an established risk factor however molecular mechanisms linking obesity and esophageal adenocarcinoma are as yet poorly understood. We found that omental adipose tissue promoted esophageal adenocarcinoma aggressiveness by increasing proliferative, migratory and invasive capacity of tumor cells via upregulation of focal adhesion and endothelial mesenchymal transition pathways with concurrent down regulation of tumor suppressor pathways.

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 5185.