Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer.
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.
Tahir
S A
SA
Scott Department of Urology, Baylor College of Medicine, 6560 Fannin Street, Houston, Texas 77030, USA.
Yang
G
G
Ebara
S
S
Timme
T L
TL
Satoh
T
T
Li
L
L
Goltsov
A
A
Ittmann
M
M
Morrisett
J D
JD
Thompson
T C
TC
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D051242:Caveolin 1; D022461:Caveolins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D017077:Culture Media, Conditioned; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000726:Androgen Antagonists; D000906:Antibodies; D018931:Antineoplastic Agents, Hormonal; C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D017077:Culture Media, Conditioned