4.8 Article

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

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 189, Issue -, Pages 72-79

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.06.010

Keywords

Ephrin receptor A10; Antibody drug; Triple negative breast cancer; Cell proliferation

Funding

  1. Project for Development of Innovative Research on Cancer Therapeutics
  2. Ministry of Education, Culture, Sports, Science and Technology of Japan
  3. Japan Society for the Promotion of Science
  4. Health Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan
  5. [26430180]

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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.

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