Abstract 3378: E-cadherin suppresses breast cancer cell growth and interleukin-6 production

Abstract

Abstract Carcinomas arise from epithelial tissues and represent the most common type of human cancer. E-cadherin is an epithelial-specific intercellular adhesion molecule, which localizes to epithelial cell adherens junctions and is a critical mediator of carcinoma cell invasion and metastasis. Although impaired E-cadherin expression can be clinically utilized to predict breast cancer cell invasiveness, metastasis, and patient survival, E-cadherin has received less attention for its role as a putative regulator of epithelial cell growth. We have previously shown that interleukin-6 (IL-6), a pleiotropic inflammatory cytokine associated with poor clinical outcome in breast cancer patients, is a potent growth factor and repressor of E-cadherin in human breast cancer cells. Consistent with clinical reports and our previous findings, we hypothesized that E-cadherin repression may be responsible for IL-6-induced breast cancer cell growth. The current study demonstrated that IL-6 enhanced the growth rates of estrogen receptor-alpha (ERα)-positive breast cancer cells in a three-dimensional (3D) tumor growth assay (TGA) in a dose-dependent manner. We showed that IL-6 also repressed E-cadherin protein levels in ERα-positive breast cancer cells in a 3D TGA in a dose-dependent manner. We have previously shown that IL-6 treatment does not affect E-cadherin-negative MDA-MB-231 cell growth, and the current study showed similar results in MCF-7 cells which express Twist and therefore lack E-cadherin. MDA-MB-231 cells lack E-cadherin and express IL-6, thus allowing us to express stable ectopic E-cadherin to evaluate its impact on cell growth and IL-6 production. Ectopic E-cadherin expression significantly suppressed MDA-MB-231 cell growth (P-value < 0.005) and IL-6 production (P-value < 0.00005) as measured by 3D TGA and ELISA, respectively. Our current findings reveal an association between enhanced breast cancer cell growth and E-cadherin repression following exposure to IL-6. Furthermore, we demonstrated that E-cadherin suppresses breast cancer cell growth and IL-6 production, which suggests a positive feedback loop in which IL-6 promotes E-cadherin repression, thereby inducing autocrine IL-6 production in breast cancer cells. 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 3378.