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


METHODS
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.
Fu
Maoyong
M
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Maresh
Erin L
EL
Soslow
Robert A
RA
Alavi
Mohammad
M
Mah
Vei
V
Zhou
Qin
Q
Iasonos
Alexia
A
Goodglick
Lee
L
Gordon
Lynn K
LK
Braun
Jonathan
J
Wadehra
Madhuri
M
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007128:Immunoglobulin Fragments / Q000494:pharmacology; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C486403:EMP2 protein, human; D007128:Immunoglobulin Fragments; D008562:Membrane Glycoproteins