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Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance.

Publication ,  Journal Article
Tanaka, H; Kono, E; Tran, CP; Miyazaki, H; Yamashiro, J; Shimomura, T; Fazli, L; Wada, R; Huang, J; Vessella, RL; An, J; Horvath, S ...
Published in: Nat Med
December 2010

The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin-specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

December 2010

Volume

16

Issue

12

Start / End Page

1414 / 1420

Location

United States

Related Subject Headings

  • Prostatic Neoplasms
  • Neoplasm Metastasis
  • Mice, SCID
  • Mice
  • Male
  • Interleukin-8
  • Immunotherapy
  • Immunology
  • Immunohistochemistry
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tanaka, H., Kono, E., Tran, C. P., Miyazaki, H., Yamashiro, J., Shimomura, T., … Reiter, R. E. (2010). Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med, 16(12), 1414–1420. https://doi.org/10.1038/nm.2236
Tanaka, Hiroshi, Evelyn Kono, Chau P. Tran, Hideyo Miyazaki, Joyce Yamashiro, Tatsuya Shimomura, Ladan Fazli, et al. “Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance.Nat Med 16, no. 12 (December 2010): 1414–20. https://doi.org/10.1038/nm.2236.
Tanaka H, Kono E, Tran CP, Miyazaki H, Yamashiro J, Shimomura T, et al. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med. 2010 Dec;16(12):1414–20.
Tanaka, Hiroshi, et al. “Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance.Nat Med, vol. 16, no. 12, Dec. 2010, pp. 1414–20. Pubmed, doi:10.1038/nm.2236.
Tanaka H, Kono E, Tran CP, Miyazaki H, Yamashiro J, Shimomura T, Fazli L, Wada R, Huang J, Vessella RL, An J, Horvath S, Gleave M, Rettig MB, Wainberg ZA, Reiter RE. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med. 2010 Dec;16(12):1414–1420.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

December 2010

Volume

16

Issue

12

Start / End Page

1414 / 1420

Location

United States

Related Subject Headings

  • Prostatic Neoplasms
  • Neoplasm Metastasis
  • Mice, SCID
  • Mice
  • Male
  • Interleukin-8
  • Immunotherapy
  • Immunology
  • Immunohistochemistry
  • Humans