Abstract 4621: EMP2 regulates the tumor microenvironment and is a novel therapeutic target for triple negative breast cancer

Breast cancer remains the most common malignancy in women, with the aggressive triple negative subtype accounting for nearly half of all breast cancer deaths. In this abstract, we describe a novel tetraspan protein, epithelial membrane protein-2 (EMP2) that is highly expressed in the majority of breast cancer tumors examined compared to healthy mammary epithelium. In particular, high levels of EMP2 were observed in over 70% of triple negative breast cancer cases examined. In tumor cells, EMP2 altered the integrin expression profile as well as promoted endothelial cell migration and tube formation through upregulation of VEGF. We produced a fully human intact IgG1 to test their effect on EMP2 expressing breast cancer cell lines. In vitro treatment with anti-EMP2 IgG1 decreased Src and FAK activation and resulted in cell death. Moreover, cultured supernatant from treated cells reduced endothelial cell migration and capillary-like tube formation. To determine the in vivo efficacy of EMP2 treatment, we first characterized potential toxicity from systemic administration. Anti-EMP2 IgG1 produced no observable toxicity (weight, CBC counts, tissue pathology) when administered at 10mg/kg over 7 weeks. Using similar conditions in preclinical xenograft and syngeneic mouse models, anti-EMP2 IgG1 decreased tumor growth with induction of necrosis. This effect was specific as no difference in tumor size was observed in EMP2 negative (Ramos) cell tumors. As in vitro and in vivo cytotoxicity was observed in both triple negative cell lines as well as cells expressing estrogen and progesterone receptors and/or Her-2/neu, these results present compelling evidence that EMP2 is a novel therapeutic target in triple negative breast cancers as well as other variants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4621. doi:1538-7445.AM2012-4621