Saling Mark, Duckett Jordan K, Ackers Ian, Coschigano Karen, Jenkinson Scott, Malgor Ramiro
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.
Interdisciplinary Program in Molecular and Cellular Biology, Ohio University, Athens, Ohio, USA.
Oncotarget. 2017 May 9;8(19):31655-31665. doi: 10.18632/oncotarget.15877.
Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines.Formalin fixed and paraffin embedded transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E-cadherin. In addition, in vitro studies using UC cell lines were investigated for Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression. The IHC results showed a correlation between the expression of Wnt5a, Ror2 and CTHRC1 with high histological grade of the tumor, while E-cadherin showed an opposite trend of expression. Real time RT-PCR results showed that RNA expression of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that the high grade cell lines exhibited signs of EMT.These findings support that Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a prognostic marker and provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools.
膀胱癌是男性中第四常见的癌症，也是泌尿道最常见的恶性肿瘤。早期发现的膀胱癌五年生存率非常高，但在局部转移后才被发现时，生存率仅约为50%。我们的研究小组最近报告称，Wnt蛋白家族成员Wnt5a的表达与尿路上皮癌（UC）的组织病理学分级和分期之间存在正相关。本研究的目的是分析俄亥俄州雅典市报告的UC病例，并研究UC人体组织样本和UC细胞系中Wnt5a/平面细胞极性（PCP）信号通路的主要成分。对福尔马林固定、石蜡包埋的经尿道切除组织进行Wnt5a、Ror-2、CTHRC1和E-钙黏蛋白的免疫染色。此外，对使用UC细胞系的体外研究进行了Wnt5a/PCP信号传导和上皮-间质转化（EMT）基因表达的研究。免疫组化结果显示，Wnt5a、Ror2和CTHRC1的表达与肿瘤的高组织学分级相关，而E-钙黏蛋白则呈现相反的表达趋势。实时逆转录-聚合酶链反应结果显示，Wnt5a/PCP通路基因的RNA表达在低级别和高级别UC细胞系中有所不同，并且高级别细胞系表现出EMT的迹象。这些发现支持Wnt5a-Ror2信号传导在UC中发挥作用，支持将Wnt5a用作预后标志物的潜力，并提供证据表明Wnt5a信号传导可作为新型治疗工具的有效分子靶点。
