Suppression of DHT-induced paracrine stimulation of endothelial cell growth by estrogens via prostate cancer cells.
Suppression of DHT-induced paracrine stimulation of endothelial cell growth by estrogens via prostate cancer cells.
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DOI：
10.1002/pros.22654
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发表时间：
2013-07
期刊：
影响因子：
2.8
通讯作者：
Zhu, Yuan-Shan
中科院分区：
文献类型：
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作者：
Wen, Juan;Zhao, Yuan;Li, Jinghe;Weng, Chunyan;Cai, Jingjing;Yang, Kan;Yuan, Hong;Imperato-McGinley, Julianne;Zhu, Yuan-Shan
前列腺癌血管生成的雄激素调节可能不是由雄激素受体（AR）直接介导的，因为在前列腺内皮细胞中未检测到AR。我们在不表达AR的小鼠内皮细胞系（MEC）中检测了前列腺肿瘤细胞对细胞增殖的旁分泌刺激以及雄激素和雌激素对其的调节。从LAPC-4或LNCaP前列腺肿瘤细胞中收集的肿瘤细胞条件培养基（TCM）对MEC细胞生长的诱导作用具有时间和浓度依赖性，与TCM中VEGF浓度相似。用双氢睾酮（DHT）治疗前列腺肿瘤细胞可促进中药诱导的mec细胞生长。VEGF受体特异性拮抗剂SU5416完全阻断中药对mec的刺激和dht增强作用。在前列腺肿瘤细胞中，17α-雌二醇或17β-雌二醇与DHT共给药完全抑制DHT增强作用，而DHT、17α-雌二醇或17β-雌二醇对mec没有明显的直接作用。此外，17α-雌二醇或17β-雌二醇可显著降低肿瘤组织中微血管的数量。我们的研究表明前列腺肿瘤细胞通过旁分泌机制调节内皮细胞的生长，该机制主要由VEGF介导；DHT可以通过肿瘤细胞调节内皮细胞的生长，而17α-雌二醇和17β-雌二醇可以抑制DHT的生长。因此，17α-雌二醇和17β-雌二醇都是雄激素反应性前列腺癌抗血管生成治疗的潜在药物。
Androgen modulation of angiogenesis in prostate cancer may be not directly mediated by androgen receptor (AR) as AR is not detected in the prostatic endothelial cells. We examined the paracrine stimulation of cell proliferation by prostate tumor cells and its modulation by androgen and estrogens in a murine endothelial cell line (MEC) that does not express AR. Tumor cell conditioned media (TCM) collected from LAPC-4 or LNCaP prostatic tumor cells produced a time- and concentration-dependent induction of cell growth in MECs, which was parallel to the VEGF concentration in the TCM. This TCM-induced cell growth in MECs was enhanced by the treatment of prostatic tumor cells with dihydrotestosterone (DHT). Both the TCM-stimulation and DHT-enhancement effects in MECs were completely blocked by SU5416, a specific VEGF receptor antagonist. Co-administration of 17α-estradiol or 17β-estradiol with DHT in prostatic tumor cells completely inhibited the DHT-enhancement effect while treatment with DHT, 17α-estradiol or 17β-estradiol did not produce any significant direct effect in MECs. Moreover, administration of 17α-estradiol or 17β-estradiol in xenograft animals with LAPC-4 or LNCaP prostate tumor significantly decreased the microvessel number in the tumor tissues. Our study indicated that prostate tumor cells regulate endothelial cell growth through a paracrine mechanism, which is mainly mediated by VEGF; and DHT is able to modulate endothelial cell growth via tumor cells, which is inhibited by 17α-estradiol and 17β-estradiol. Thus, both17α-estradiol and 17β-estradiol are potential agents for anti-angiogenesis therapy in androgen-responsive prostate cancer.
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DOI：
10.1158/1078-0432.ccr-08-2660
发表时间：
2009-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Knudsen KE;Scher HI
通讯作者：
Scher HI
DOI：
10.1016/j.juro.2010.09.008
发表时间：
2011-01
期刊：
The Journal of urology
影响因子：
--
作者：
Qiao Y;Wang L;Cai LQ;Tan C;Imperato-McGinley J;Zhu YS
通讯作者：
Zhu YS
DOI：
10.1152/ajpheart.00823.2007
发表时间：
2008-04-01
影响因子：
4.8
作者：
Crabtree, Mark J.;Smith, Caroline L.;Gross, Steven S.
通讯作者：
Gross, Steven S.
影响因子：
4.8
作者：
Franck-Lissbrant, I;Häggström, S;Bergh, A
通讯作者：
Bergh, A
影响因子：
2.9
作者：
Okihara, K;Watanabe, H;Kojima, M
通讯作者：
Kojima, M