Possible role of sonic hedgehog and epithelial-mesenchymal transition in renal cell cancer progression.
Possible role of sonic hedgehog and epithelial-mesenchymal transition in renal cell cancer progression.
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DOI：
10.4111/kju.2013.54.8.547
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Fujisawa M
中科院分区：
文献类型：
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作者：
Behnsawy HM;Shigemura K;Meligy FY;Yamamichi F;Yamashita M;Haung WC;Li X;Miyake H;Tanaka K;Kawabata M;Shirakawa T;Fujisawa M
已知Sonic hedgehog（Shh）信号传导和上皮-间质转化（EMT）都与癌症进展有关。本研究的目的是探讨Shh信号和EMT在肾细胞癌（RCC）中的作用。在存在或不存在Shh信号传导刺激剂、重组Shh（r-Shh）蛋白或Shh信号传导抑制剂环巴胺的情况下，在RCC细胞系中测定细胞增殖。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）检测EMT标志物（E-cadherin、N-cadherin和vimentin）和骨粘连蛋白的表达。肾癌患者肾切除标本中Ki-67、Gli-1、骨粘连蛋白和EMT标记物的表达也通过免疫组织化学（IHC）染色进行测定。RCC细胞显示r-Shh蛋白增强的细胞增殖，而细胞增殖被抑制通过在RenCa细胞中加入环巴胺。实时定量RT-PCR显示r-Shh抑制了RenCa细胞中E-cadherin的表达，并且这种抑制作用部分被单独的环巴胺阻断。在IHC结果中，骨连接蛋白与静脉窦浸润显著相关（p=0.0218），波形蛋白的表达与淋巴管浸润显著相关（p=0.0392）。Shh信号和EMT在肾细胞癌的发生发展中起重要作用，Shh信号抑制剂环巴胺可能成为肾细胞癌的分子靶向治疗策略。
Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) are both known to relate to cancer progression. The purpose of this study was to investigate the role of Shh signaling and EMT in renal cell carcinoma (RCC). Cell proliferation was assayed in RCC cell lines in the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh) protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin. The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy specimens from RCC patients was also measured by immunohistochemical (IHC) staining. RCC cells showed enhanced cell proliferation by r-Shh protein, whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin and that this suppression was partly blocked by cyclopamine alone in RenCa cells. In the IHC results, osteonectin significantly correlated with vein sinus invasion (p=0.0218), and the expression of vimentin significantly correlated with lymphatic invasion (p=0.0392). Shh signaling and EMT play roles in RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible molecular targeted therapeutic strategy for RCC.