Functional analysis of secreted caveolin-1 in mouse models of prostate cancer progression

Masami Watanabe, Guang Yang, Guangwen Cao, Salahaldin A. Tahir, Koji Naruishi, Ken Ichi Tabata, Elmoataz Abdel Fattah, Kartik Rajagopalan, Terry L. Timme, Sanghee Park, Shinji Kurosaka, Kohei Edamura, Ryuta Tanimoto, Francesco J. Demayo, Alexei A. Goltsov, Timothy C. Thompson

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34 Citations (Scopus)

Abstract

Previously, we reported that caveolin-1 (cav-1) is overexpressed in metastatic prostate cancer and that virulent prostate cancer cells secrete biologically active cav-1. We also showed that cav-1 expression leads to prosurvival activities through maintenance of activated Akt and that cav-1 is taken up by other cav-1-negative tumor cells and/or endothelial cells, leading to stimulation of angiogenic activities through PI-3-K-Akt-eNOS signaling. To analyze the functional consequences of cav-1 overexpression on the development and progression of prostate cancer in vivo, we generated PBcav-1 transgenic mice. Adult male PBcav-1 mice showed significantly increased prostatic wet weight and higher incidence of epithelial hyperplasia compared with nontransgenic littermates. Increased immunostaining for cav-1, proliferative cell nuclear antigen, P-Akt, and reduced nuclear p27Kip1 staining occurred in PBcav-1 hyperplastic prostatic lesions. PBcav-1 mice showed increased resistance to castration-induced prostatic regression and elevated serum cav-1 levels compared with nontransgenic littermates. Intraprostatic injection of androgen-sensitive, cav-1-secreting RM-9 mouse prostate cancer cells resulted in tumors that were larger in PBcav-1 mice than in nontransgenic littermates (P = 0.04). Tail vein inoculation of RM-9 cells produced significantly more experimental lung metastases in PBcav-1 males than in nontransgenic male littermates (P = 0.001), and in cav-1+/+ mice than in cav-1-/- mice (P = 0.041). Combination treatment with surgical castration and systemic cav-1 antibody dramatically reduced the number of experimental metastases. These experimental data suggest a causal association of secreted cav-1 and prostate cancer growth and progression.

Original languageEnglish
Pages (from-to)1446-1455
Number of pages10
JournalMolecular Cancer Research
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Watanabe, M., Yang, G., Cao, G., Tahir, S. A., Naruishi, K., Tabata, K. I., Fattah, E. A., Rajagopalan, K., Timme, T. L., Park, S., Kurosaka, S., Edamura, K., Tanimoto, R., Demayo, F. J., Goltsov, A. A., & Thompson, T. C. (2009). Functional analysis of secreted caveolin-1 in mouse models of prostate cancer progression. Molecular Cancer Research, 7(9), 1446-1455. https://doi.org/10.1158/1541-7786.MCR-09-0071