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Clin Cancer Res. 2010 Aug 1;16(15):3954-63. doi: 10.1158/1078-0432.CCR-10-0368.

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

Author information

  • 1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Abstract

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.

(c) 2010 AACR.

PMID:
20670949
[PubMed - indexed for MEDLINE]
PMCID:
PMC2913478
Free PMC Article

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