Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Clin Cancer Res. 2010 Aug 1;16(15):3954-63. doi: 10.1158/1078-0432.CCR-10-0368.
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 >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.
These findings indicate that EMP2 is expressed in the majority of ovarian tumors and may be a feasible target in vivo.
四跨膜蛋白上皮膜蛋白-2（EMP2）已被证明可以调节特定整合素对的表面显示和信号转导，最近它被确定为人类子宫内膜癌的一种预后生物标志物。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分析技术检查了卵巢癌患者群体中 EMP2 的表达。我们评估了 EMP2 定向抗体治疗的疗效，使用了完全人源重组二价抗体片段（二抗）在体外和卵巢癌异种移植模型体内。
与非恶性卵巢上皮相比，我们在人类卵巢癌组织微阵列中发现 EMP2 在 >70%的浆液性和子宫内膜样卵巢肿瘤中高度表达。使用抗 EMP2 二抗，我们评估了具有可检测 EMP2 表达的 9 个人类卵巢癌细胞系的体外反应。抗 EMP2 二抗处理人类卵巢癌细胞系诱导细胞死亡和细胞生长迟缓，这些反应率与细胞 EMP2 表达相关。我们接下来评估了抗 EMP2 二抗在携带卵巢子宫内膜样癌细胞系 OVCAR5 异种移植物的小鼠中的作用。抗 EMP2 二抗显著抑制 OVCAR5 异种移植物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，并且可能是体内可行的靶标。
