Expression Profile of WNT Molecules in Prostate Cancer and its Regulation by Aminobisphosphonates
Expression Profile of WNT Molecules in Prostate Cancer and its Regulation by Aminobisphosphonates
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DOI：
10.1002/jcb.23070
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发表时间：
2011-06-01
影响因子：
4
通讯作者：
Hofbauer, Lorenz C.
中科院分区：
文献类型：
--
作者：
Thiele, Sylvia;Rauner, Martina;Hofbauer, Lorenz C.
骨骼转移代表晚期前列腺癌（PCA）患者的常见并发症，通常需要双膦酸盐治疗以限制骨骼相关事件。转移的PCA细胞干扰骨头重塑。由于Wnt信号通路调节骨骼重塑，并与肿瘤进展和骨质映射有关，因此我们分析了原代PCA组织和PCA细胞系的Wnt谱，并评估了双膦酸酯的调节。从良性前列腺增生（BPH）和具有不同疾病阶段的PCA患者中获得了前列腺组织（n = 18）。从62例患者中收集血清样品。 17例用唑来膦酸治疗的17例患者存在骨骼转移。在组织RNA提取物和血清样品以及骨骼（PC3）和非稳态（DU145，LNCAP）PCA细胞系中分析了Bisphoshonates的WNT谱及其调节。 WNT途径的几个成员，包括WNT5A，FZD5和DKK1在PCA组织中高度上调了晚期PCA患者。有趣的是，与非稳态细胞相比，骨质细胞显示出明显的Wnt曲线。虽然在PC3细胞中高度表达Wnt5a，FZD5和DKK1，但在DU145细胞中，Wnt1和SFRP1 mRNA水平较高。此外，PC3细胞中的唑来膦酸下调WNT5A（-34％），FZD5（-60％）和DKK1（-46％）的mRNA水平下调。有趣的是，与双膦酸盐患者相比，接受唑来膦酸的骨骼转移患者的DKK1血清水平高两个。 Wnt信号通路在晚期PCA中被上调，在术中差异表达，在骨质和非骨骼的细胞中，并由唑来膦酸调节。 J. Cell。生物化学。 112：1593-1600，2011。（c）2011 Wiley-Liss，Inc。
Skeletal metastases represent a frequent complication in patients with advanced prostate cancer (PCa) and often require bisphosphonate treatment to limit skeletal-related events. Metastasized PCa cells disturb bone remodeling. Since the WNT signaling pathway regulates bone remodeling and has been implicated in tumor progression and osteomimicry, we analyzed the WNT profile of primary PCa tissues and PCa cell lines and assessed its regulation by bisphosphonates. Prostate tissue (n = 18) was obtained from patients with benign prostate hyperplasia (BPH) and PCa patients with different disease stages. Serum samples were collected from 62 patients. Skeletal metastases were present in 17 patients of whom 6 had been treated with zoledronic acid. The WNT profile and its regulation by bisphoshonates were analyzed in tissue RNA extracts and serum samples as well as in osteotropic (PC3) and non-osteotropic (DU145, LNCaP) PCa cell lines. Several members of the WNT pathway, including WNT5A, FZD5, and DKK1 were highly up-regulated in PCa tissue from patients with advanced PCa. Interestingly, osteotropic cells showed a distinct WNT profile compared to non-osteotropic cells. While WNT5A, FZD5, and DKK1 were highly expressed in PC3 cells, WNT1 and SFRP1 mRNA levels were higher in DU145 cells. Moreover, zoledronic acid down-regulated mRNA levels of WNT5A (-34%), FZD5 (-60%), and DKK1 (-46%) in PC3 cells. Interestingly, patients with skeletal metastases who received zoledronic acid had twofold higher DKK1 serum levels compared to bisphosphonate-naive patients. The WNT signaling pathway is up-regulated in advanced PCa, differentially expressed in osteotropic versus non-osteotropic cells, and is regulated by zoledronic acid. J. Cell. Biochem. 112: 1593-1600, 2011. (C) 2011 Wiley-Liss, Inc.