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

J Control Release. 2014 Sep 10;189:72-9. doi: 10.1016/j.jconrel.2014.06.010. Epub 2014 Jun 16.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Molecular Targeted Therapy
  • Receptor, ErbB-2 / metabolism
  • Receptors, Eph Family / genetics
  • Receptors, Eph Family / immunology
  • Receptors, Eph Family / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Testis / metabolism
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Receptors, Estrogen
  • Receptors, Progesterone
  • EPHA10 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Receptors, Eph Family