Secreted caveolin-1 stimulates cell survival/clonal growth and contributesto metastasis in androgen-insensitive prostate cancer

Caveolin-1 is an integral protein of caveolae, known to play important role s in signal transduction and lipid transport. We demonstrate that caveolin- 1 expression is significantly increased in primary and metastatic human pro state cancer after androgen ablation therapy, We also show that caveolin-1 is secreted by androgen-insensitive prostate cancer cells, and that this se cretion is regulated by steroid hormones, Significantly, caveolin-1 was det ected in the MDL, fraction of serum specimens from patients with advanced p rostate cancer and to a lesser extent in normal subjects. Conditioned media from high passage caveolin-1 secreting, androgen-insensitive, LNCaP cells stimulated increased viability and clonal growth of low passage, caveolin-1 -negative, androgen-sensitive, LNCaP cells in vitro, and this effect was bl ocked by treating the media with caveolin-1 antibody. i.p. injections of ca veolin-1 antibody suppressed the orthotopic growth and spontaneous metastas is of highly metastatic, androgen-insensitive caveolin-1-secreting mouse pr ostate cancer. Overall, our results establish caveolin-1 as an autocrine/pa racrine factor that is associated with androgen-insensitive prostate cancer , We demonstrate the potential for caveolin-1 as a therapeutic target for t his important malignancy.