Abstract 2512: Epothilone B enhances surface EpCAM expression in ovarian cancer cells

Abstract

Abstract OBJECTIVES Epothilone B (EpoB), like Taxol, induces tubulin polymerization and microtubule stabilization resulting in an inhibition of microtubule dynamic instability. The drug is presently being evaluated in phase III clinical trials. An EpoB analog Ixabepilone, has been approved by the FDA for the treatment of metastatic breast cancer. Epithelial cell adhesion antigen (EpCAM) expression is significantly higher in epithelial ovarian cancer cells compared to normal cells. METHODS We used biochemical methods, immunofluorescence and flow cytometry to identify EpCAM expression on the surface of the ovarian cancer cell line, Hey, after exposure to EpoB. We also investigated the relationship between EpoB-mediated surface EpCAM expression and EpoB-induced tubulin acetylation in Hey cells. RESULTS We investigated the effect of EpoB and other microtubule-interacting agents on surface EpCAM expression and found that nanomolar concentrations of EpoB, Taxol, discodermolide or vinblastine caused a marked increase in surface EpCAM expression in an ovarian cancer cell line, Hey. Alpha-tubulin acetylation, a surrogate marker for stable microtubules, was increased following treatment with Taxol, EpoB and discodermolide, but not with vinblastine, indicating that drug-enhanced surface EpCAM expression does not correlate with tubulin acetylation or stabilization. Unexpectedly, EpoB did not have a significant effect on EpCAM mRNA expression, nor did it alter the level of total cellular EpCAM in the human ovarian cancer cell line. CONCLUSIONS Our results suggest that disruption of the microtubule cytoskeleton is associated with the redistribution of cell surface antigens in ovarian cancer cells. The increase in cell surface EpCAM antigen density may facilitate the antibody targeting of EpCAM-positive ovarian 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 2512.