Abstract 5177: Assessment of EpCAM function in lung cancer progression

Abstract

Abstract The epithelial cell adhesion molecule (EpCAM) is expressed on the basolateral membrane of the majority of epithelial tissues and it is upregulated or expressed de novo in various carcinomas. Several studies showed that high level EpCAM expression is associated with poor survival and tumor grading. EpCAM remains an attractive cancer therapeutic target. Until recently, however, molecular impact of EpCAM on cancer signaling processes and growth regulation has not been clearly understood. We show here that inhibition of EpCAM by inducible shRNA resulted in a change of cell cycle profile and decreased cellular proliferation in non-small cell lung cancer cells. Cancer cells were apparently arrested in G1 phase, and subsequent western blotting experiments showed that p27 protein increased upon EpCAM inhibition. To test whether EpCAM depletion would also lead to changes in tumor progression in vivo, we assessed the effect of EpCAM shRNA induction in lung cancer animal xenograft model. EpCAM knock-down led to almost complete tumor progression in vivo. Additional studies showed that inhibition of EpCAM expression was related to decreased microvessel density, revealed by CD31 immunohistochemical staining. Overall, the data presented here suggest that EpCAM can be another therapeutic target of lung cancer. Development of inhibitory modality of EpCAM function needs to be tested further alone or in combination of other therapeutic reagents. 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 5177.