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Fu, M. et al.

Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer.

PURPOSE: The tetraspan protein epithelial membrane protein-2 (EMP2) has been shown to regulate the surface display and signaling from select integrin pairs, and it was recently identified as a prognostic biomarker in human endometrial cancer. In this study, we assessed the role of EMP2 in human ovarian cancer. EXPERIMENTAL DESIGN: We examined the expression of EMP2 within a population of women with ovarian cancer using tissue microarray assay technology. We evaluated the efficacy of EMP2-directed antibody therapy using a fully human recombinant bivalent antibody fragment (diabody) in vitro and ovarian cancer xenograft models in vivo. RESULTS: EMP2 was found to be highly expressed in >70% of serous and endometrioid ovarian tumors compared with nonmalignant ovarian epithelium using a human ovarian cancer tissue microarray. Using anti-EMP2 diabody, we evaluated the in vitro response of nine human ovarian cancer cell lines with detectable EMP2 expression. Treatment of human ovarian cancer cell lines with anti-EMP2 diabodies induced cell death and retarded cell growth, and these response rates correlated with cellular EMP2 expression. We next assessed the effects of anti-EMP2 diabodies in mice bearing xenografts from the ovarian endometrioid carcinoma cell line OVCAR5. Anti-EMP2 diabodies significantly suppressed tumor growth and induced cell death in OVCAR5 xenografts. CONCLUSIONS: These findings indicate that EMP2 is expressed in the majority of ovarian tumors and may be a feasible target in vivo.[1]

References

Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer. Fu, M., Maresh, E.L., Soslow, R.A., Alavi, M., Mah, V., Zhou, Q., Iasonos, A., Goodglick, L., Gordon, L.K., Braun, J., Wadehra, M. Clin. Cancer Res. (2010) [Pubmed]

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