Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer Journal Article
| Authors: | 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. |
| Article Title: | Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer |
| 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. ©2010 AACR. |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; protein expression; aged; middle aged; unclassified drug; human cell; major clinical study; drug efficacy; nonhuman; antineoplastic agents; drug targeting; endometrioid carcinoma; ovarian neoplasms; mouse; animals; mice; animal tissue; cell death; cancer immunotherapy; ovary cancer; gene expression; gene expression profiling; animal experiment; animal model; in vivo study; cancer cell culture; in vitro study; tumor xenograft; xenograft model antitumor assays; cancer inhibition; blotting, western; immunotherapy; recombinant antibody; mice, nude; membrane glycoproteins; tissue array analysis; tissue microarray; epithelial membrane protein 2; recombinant bivalent antibody fragment a10; recombinant bivalent antibody fragment ks49; recombinant bivalent antibody fragment ks83; tetraspanin; immunoglobulin fragments |
| Journal Title: | Clinical Cancer Research |
| Volume: | 16 |
| Issue: | 15 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-08-01 |
| Start Page: | 3954 |
| End Page: | 3963 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-10-0368 |
| PUBMED: | 20670949 |
| PROVIDER: | scopus |
| PMCID: | PMC2913478 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus" |
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