Abstract 3038: Epithelial Membrane Protein-2 (EMP2) promotes glioblastoma growth via upregulating invasion and angiogenesis.

Abstract

Abstract Recent data suggests that EMP2 is a novel oncogene in a number of tumors including breast, ovarian, endometrial and primary central nervous system malignancies. Its expression correlates with poor survival and can serve as a prognostic indicator in many tumors. Glioblastoma multiforme (GBM) is an aggressive brain tumor with a medium survival of 18 months, and we have found that EMP2 is expressed in the majority of GBM tumors but not in healthy brains. In order to therapeutically exploit the expression of EMP2 on these tumors, we have developed recombinant antibodies to this oncogene. In experimental models, use of the anti-EMP2 antibodies showed profound efficacy in reducing GBM tumor load. We further dissected the underlying molecular mechanisms and found that EMP2 accelerated GBM tumor growth through increasing αvβ3 integrin surface expression in GBM cells, activating downstream FAK and Src kinases and promoting cell migration and invasion. Furthermore, EMP2 upregulated vascular endothelial growth factor (VEGF) in several GBM cell lines. This increase appeared to be functionally relevant as conditioned medium from GBM cells with forced overexpression of EMP2 increased human umbilical vein endothelial cell (HUVEC) migration and capillary tube formation, suggesting a role for EMP2 in the regulation of tumor angiogenesis. Our results suggest the importance of this oncogene in the control of the tumor microenvironment and that targeting EMP2 expression may be a novel therapy for GBM. Citation Format: Yu Qin. Epithelial Membrane Protein-2 (EMP2) promotes glioblastoma growth via upregulating invasion and angiogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3038. doi:10.1158/1538-7445.AM2013-3038