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

Abstract:

:Caveolin-1 is an integral protein of caveolae, known to play important roles in signal transduction and lipid transport. We demonstrate that caveolin-1 expression is significantly increased in primary and metastatic human prostate cancer after androgen ablation therapy. We also show that caveolin-1 is secreted by androgen-insensitive prostate cancer cells, and that this secretion is regulated by steroid hormones. Significantly, caveolin-1 was detected in the MDL(3) fraction of serum specimens from patients with advanced prostate 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 blocked by treating the media with caveolin-1 antibody. i.p. injections of caveolin-1 antibody suppressed the orthotopic growth and spontaneous metastasis of highly metastatic, androgen-insensitive caveolin-1-secreting mouse prostate cancer. Overall, our results establish caveolin-1 as an autocrine/paracrine factor that is associated with androgen-insensitive prostate cancer. We demonstrate the potential for caveolin-1 as a therapeutic target for this important malignancy.

journal_name

Cancer Res

journal_title

Cancer research

authors

Tahir SA,Yang G,Ebara S,Timme TL,Satoh T,Li L,Goltsov A,Ittmann M,Morrisett JD,Thompson TC

subject

Has Abstract

pub_date

2001-05-15 00:00:00

pages

3882-5

issue

10

eissn

0008-5472

issn

1538-7445

journal_volume

61

pub_type

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