Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer

Salahaldin A. Tahir, Guang Yang, Alexei A. Goltsov, Masami Watanabe, Ken Ichi Tabata, Josephine Addai, El Moataz Abdel Fattah, Dov Kadmon, Timothy C. Thompson

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Caveolin, a major structural component of specialized plasma membrane invaginations (caveolae) that participate in diverse cellular activities, has been implicated in the pathogenesis of several human diseases, including cancer. We showed in earlier studies that caveolin-1 (cav-1) is consistently and strongly overexpressed in metastatic prostate cancer and is secreted in a biologically active form by virulent prostate cancer cells. Using both in vitro and in vivo model systems, we now present evidence supporting a proangiogenic role for cav-1 in prostate cancer development and progression. Recombinant cav-1 (rcav-1) was taken up by cav-1-/- endothelial cells through either a lipid raft/caveolae- or clathrin-dependent mechanism, leading to specific angiogenic activities (tubule formation, cell migration, and nitric oxide production) that were mediated by rcav-1 stimulation of the PI3K-Akt-eNOS signaling module. Pathologic angiogenesis induced by cav-1 in prostate cancer-bearing mice correlated with an increased frequency, number, and size of lung metastases. We propose that in addition to its antiapoptotic role, cav-1 secreted by prostate cancer cells functions critically as a proangiogenic factor in metastatic progression of this tumor. These new insights into cav-1 function in prostate cancer may provide a base for the design of clinically applicable therapeutic strategies.

Original languageEnglish
Pages (from-to)731-739
Number of pages9
JournalCancer Research
Volume68
Issue number3
DOIs
Publication statusPublished - Feb 1 2008
Externally publishedYes

Fingerprint

Caveolin 1
Prostatic Neoplasms
Neoplasms
Caveolae
Pathologic Neovascularization
Caveolins
Clathrin
Phosphatidylinositol 3-Kinases
Cell Movement
Nitric Oxide
Endothelial Cells
Cell Membrane
Neoplasm Metastasis
Lipids
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tahir, S. A., Yang, G., Goltsov, A. A., Watanabe, M., Tabata, K. I., Addai, J., ... Thompson, T. C. (2008). Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer. Cancer Research, 68(3), 731-739. https://doi.org/10.1158/0008-5472.CAN-07-2668

Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer. / Tahir, Salahaldin A.; Yang, Guang; Goltsov, Alexei A.; Watanabe, Masami; Tabata, Ken Ichi; Addai, Josephine; Fattah, El Moataz Abdel; Kadmon, Dov; Thompson, Timothy C.

In: Cancer Research, Vol. 68, No. 3, 01.02.2008, p. 731-739.

Research output: Contribution to journalArticle

Tahir, SA, Yang, G, Goltsov, AA, Watanabe, M, Tabata, KI, Addai, J, Fattah, EMA, Kadmon, D & Thompson, TC 2008, 'Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer', Cancer Research, vol. 68, no. 3, pp. 731-739. https://doi.org/10.1158/0008-5472.CAN-07-2668
Tahir, Salahaldin A. ; Yang, Guang ; Goltsov, Alexei A. ; Watanabe, Masami ; Tabata, Ken Ichi ; Addai, Josephine ; Fattah, El Moataz Abdel ; Kadmon, Dov ; Thompson, Timothy C. / Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer. In: Cancer Research. 2008 ; Vol. 68, No. 3. pp. 731-739.
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