Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer.
Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer.
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DOI：
10.1158/1078-0432.ccr-10-0368
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发表时间：
2010-08-01
期刊：
影响因子：
--
通讯作者：
Wadehra M
中科院分区：
文献类型：
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作者：
Fu M;Maresh EL;Soslow RA;Alavi M;Mah V;Zhou Q;Iasonos A;Goodglick L;Gordon LK;Braun J;Wadehra M
四跨蛋白上皮膜蛋白 2 (EMP2) 已被证明可以调节精选整合素对的表面展示和信号传导，最近被确定为人类子宫内膜癌的预后生物标志物。在这项研究中，我们评估了 EMP2 在人类卵巢癌中的作用。我们使用组织微阵列检测技术检查了卵巢癌女性群体中 EMP2 的表达。我们在体外使用全人重组二价抗体片段（双抗体）和体内卵巢癌异种移植模型评估了 EMP2 导向抗体治疗的疗效。使用人卵巢癌组织微阵列发现，与非恶性卵巢上皮细胞相比，EMP2 在超过 70% 的浆液性和子宫内膜样卵巢肿瘤中高表达。使用抗 EMP2 双抗体，我们评估了 9 种可检测到 EMP2 表达的人卵巢癌细胞系的体外反应。用抗EMP2双抗体处理人卵巢癌细胞系诱导细胞死亡并延缓细胞生长，并且这些反应率与细胞EMP2表达相关。接下来，我们评估了抗 EMP2 双抗体对携带卵巢子宫内膜样癌细胞系 OVCAR5 异种移植物的小鼠的影响。抗 EMP2 双抗体显着抑制 OVCAR5 异种移植物中的肿瘤生长并诱导细胞死亡。这些发现表明EMP2在大多数卵巢肿瘤中表达，并且它可能是体内可行的靶点。
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. 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. EMP2 was found to be highly expressed in over 70% of serous and endometrioid ovarian tumors compared to non-malignant ovarian epithelium using a human ovarian cancer tissue microarray. Using anti-EMP2 diabody, we evaluated the in vitro response of 9 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. These findings indicate that EMP2 is expressed in the majority of ovarian tumors and it may be a feasible target in vivo.