Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):545-9. doi: 10.1016/j.bbrc.2014.06.007. Epub 2014 Jun 9.
We recently identified Eph receptor A10 (EphA10) as a novel breast cancer-specific protein. Moreover, we also showed that an in-house developed anti-EphA10 monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer cells, suggesting EphA10 as a promising target for breast cancer therapy. However, the only other known report for EphA10 was its expression in the testis at the mRNA level. Therefore, the potency of EphA10 as a drug target against cancers other than the breast is not known. The expression of EphA10 in a wide variety of cancer cells was studied and the potential of EphA10 as a drug target was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was overexpressed in breast cancer cell lines as well as in prostate and colon cancer cell lines. Thus, we focused on prostate cancers in which EphA10 expression was equivalent to that in breast cancers. As a result, EphA10 expression was clearly shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and protein levels. In order to evaluate the potential of EphA10 as a drug target, we analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found that significant cytotoxicity was mediated by the expression of EphA10. Therefore, the idea was conceived that the overexpression of EphA10 in prostate cancers might have a potential as a target for prostate cancer therapy, and formed the basis for the studies reported here.
我们最近确定 Eph 受体 A10（EphA10）是一种新的乳腺癌特异性蛋白。此外，我们还表明，一种内部开发的抗 EphA10 单克隆抗体（mAb）显著抑制了乳腺癌细胞的增殖，这表明 EphA10 是乳腺癌治疗的一个有前途的靶点。然而，唯一其他已知的 EphA10 报告是它在睾丸中的 mRNA 水平表达。因此，EphA10 作为除乳腺癌以外的癌症的药物靶点的效力尚不清楚。研究了 EphA10 在各种癌细胞中的表达，并评估了 EphA10 作为药物靶点的潜力。EphA10 mRNA 表达的筛选表明，EphA10 在乳腺癌细胞系以及前列腺癌和结肠癌细胞系中过表达。因此，我们专注于 EphA10 表达与乳腺癌相当的前列腺癌。结果，EphA10 表达在临床前列腺肿瘤组织以及细胞系中的 mRNA 和蛋白水平上均得到了清晰显示。为了评估 EphA10 作为药物靶点的潜力，我们分析了抗 EphA10 mAb 的补体依赖性细胞毒性作用，并发现 EphA10 的表达介导了显著的细胞毒性。因此，人们认为前列腺癌中 EphA10 的过表达可能成为前列腺癌治疗的潜在靶点，这构成了这里报道的研究的基础。
