title: Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer.
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.
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Salahaldin A
authors.initials: SA
authors.lastname: Tahir
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Goltsov
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tabata
authors.forename: Josephine
authors.initials: J
authors.lastname: Addai
authors.forename: El Moataz Abdel
authors.initials: el MA
authors.lastname: Fattah
authors.forename: Dov
authors.initials: D
authors.lastname: Kadmon
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000502:physiology*; D002966:Clathrin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D014162:Transfection
chemical_list: D051242:Caveolin 1; D002966:Clathrin; D011994:Recombinant Proteins