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Title: Eph receptor A10 has a potential as a target for a prostate cancer therapy

Highlights: • EphA10 mRNA is overexpressed in breast, prostate and colon cancer cell lines. • EphA10 is overexpressed in clinical prostate tumors at mRNA and protein levels. • Anti-EphA10 antibodies were cytotoxic on EphA10-positive prostate cancer cells. - Abstract: 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 inmore » 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.« less
Authors:
 [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [2] ;  [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [1] ;  [2] ;
  1. Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan)
  2. (Japan)
  3. Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD 57104 (United States)
  4. Laboratory of Innovative Antibody Engineering and Design, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan)
Publication Date:
OSTI Identifier:
22416642
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CELL PROLIFERATION; DNA; DRUGS; HUMAN POPULATIONS; LARGE INTESTINE; MAMMARY GLANDS; MESSENGER-RNA; MONOCLONAL ANTIBODIES; NEOPLASMS; PROSTATE; RECEPTORS; SCREENING; THERAPY; TOXICITY