Ephrin receptor A10 is a promising drug target potentially useful for breast cancers including triple negative breast cancers

被引:41
作者
Nagano, Kazuya [1 ]
Maeda, Yuka [1 ,2 ]
Kanasaki, So-ichiro [1 ,2 ]
Watanabe, Takanobu [1 ,2 ]
Yamashita, Takuya [1 ,2 ]
Inoue, Masaki [1 ]
Higashisaka, Kazuma [1 ,2 ]
Yoshioka, Yasuo [1 ,2 ,3 ]
Abe, Yasuhiro [1 ]
Mukai, Yohei [4 ]
Kamada, Haruhiko [1 ,3 ]
Tsutsumi, Yasuo [2 ,3 ]
Tsunoda, Shin-ichi [1 ,2 ,3 ]
机构
[1] Natl Inst Biomed Innovat, Lab Biopharmaceut Res, Ibaraki, Osaka 5670085, Japan
[2] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan
[3] Osaka Univ, Ctr Adv Med Engn & Informat, Suita, Osaka 5650871, Japan
[4] Natl Inst Biomed Innovat, Lab Innovat Antibody Engn & Design, Ibaraki, Osaka 5670085, Japan
基金
日本学术振兴会;
关键词
Ephrin receptor A10; Antibody drug; Triple negative breast cancer; Cell proliferation; TYROSINE KINASE; TUMOR-GROWTH; METASTATIC PROGRESSION; TRASTUZUMAB RESISTANCE; EPHA2; ANGIOGENESIS; ACTIVATION; SURVIVAL; THERAPY; EPHB4;
D O I
10.1016/j.jconrel.2014.06.010
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 parentalMDA-MB-435 cells which express a lowlevel 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. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:72 / 79
页数:8
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