Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer.
Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer.
复制标题
DOI：
--
复制
发表时间：
2001-05
期刊：
影响因子：
11.2
通讯作者：
S. Tahir;Guang Yang;Shin Ebara;T. Timme;Takefumi Satoh;L. Li;A. Goltsov;M. Ittmann;J. Morrisett;Timothy C. Thompson
中科院分区：
文献类型：
--
作者：
S. Tahir;Guang Yang;Shin Ebara;T. Timme;Takefumi Satoh;L. Li;A. Goltsov;M. Ittmann;J. Morrisett;Timothy C. Thompson
Caveolin-1是Caveolae中的一种重要蛋白，在信号转导和脂质转运中起重要作用。我们证明，小窝蛋白-1的表达显着增加，在原发性和转移性人前列腺癌雄激素消融治疗后。我们还表明，小窝蛋白-1是由雄激素不敏感的前列腺癌细胞分泌，这种分泌是由类固醇激素调节。值得注意的是，小窝蛋白-1在晚期前列腺癌患者血清样本的MDL（3）部分中检测到，在正常受试者中检测到的程度较低。来自高传代小窝蛋白-1分泌的、雄激素不敏感的LNCaP细胞的条件培养基在体外刺激低传代的、小窝蛋白-1阴性的、雄激素敏感的LNCaP细胞的活力和克隆生长增加，并且这种作用通过用小窝蛋白-1抗体处理培养基来阻断。腹膜内注射小窝蛋白-1抗体抑制了高转移性、雄激素不敏感的分泌小窝蛋白-1的小鼠前列腺癌的原位生长和自发转移。总的来说，我们的研究结果确定小窝蛋白-1作为一种自分泌/旁分泌因子，与雄激素不敏感的前列腺癌相关。我们证明了小窝蛋白-1作为这种重要恶性肿瘤的治疗靶点的潜力。
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.