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.
J Control Release. 2014 Sep 10;189:72-9. doi: 10.1016/j.jconrel.2014.06.010. Epub 2014 Jun 16.
Ephrin receptor A10 (EphA10) is a relatively uncharacterized protein which is expressed in many breast cancers but not expressed in normal breast tissues. Here, we examined the potential of EphA10 as a drug target in breast cancer. Immunohistochemical staining of clinical tissue sections revealed that EphA10 was expressed in various breast cancer subtypes, including triple negative breast cancers (TNBCs), with no expression observed in normal tissues apart from testis. Ligand-dependent proliferation was observed in EphA10-transfected MDA-MB-435 cells (MDA-MB-435(EphA10)) and native TNBC cells (MDA-MB-436). However, this phenomenon was not observed in parental MDA-MB-435 cells which express a low level of EphA10. Finally, tumor growth was significantly suppressed by administration of an anti-EphA10 monoclonal antibody in a xenograft mouse model. These results suggest that inhibition of EphA10 signaling may be a novel therapeutic option for management of breast cancer, including TNBCs which are currently not treated with molecularly targeted agents.
Ephrin 受体 A10（EphA10）是一种相对未被阐明的蛋白，在许多乳腺癌中表达，但在正常乳腺组织中不表达。在这里，我们研究了 EphA10 作为乳腺癌药物靶点的潜力。临床组织切片的免疫组织化学染色显示，EphA10 在各种乳腺癌亚型中表达，包括三阴性乳腺癌（TNBC），除睾丸外，在正常组织中没有表达。在 EphA10 转染的 MDA-MB-435 细胞（MDA-MB-435(EphA10)）和天然 TNBC 细胞（MDA-MB-436）中观察到配体依赖性增殖。然而，在 EphA10 表达水平较低的亲本 MDA-MB-435 细胞中未观察到这种现象。最后，在异种移植小鼠模型中，施用抗 EphA10 单克隆抗体可显著抑制肿瘤生长。这些结果表明，抑制 EphA10 信号可能是治疗乳腺癌的一种新的治疗选择，包括目前未用分子靶向药物治疗的 TNBC。
