Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng, Beijing 100730, P.R. China.
Oncol Rep. 2018 Sep;40(3):1641-1649. doi: 10.3892/or.2018.6528. Epub 2018 Jun 27.
The aim of the present study was to research the effect of microenvironmental change on epithelial‑mesenchymal transition (EMT) in pancreatic cancer cells and to determine the correlation between E‑cadherin expression and the prognosis of pancreatic cancer patients. We established hypoxic, serum‑deficient and TGF‑β‑induced microenvironment models of pancreatic cancer cells and studied the changes in the mRNA and protein expression of EMT‑related molecules, E‑cadherin and vimentin, using western blot analysis and real‑time PCR. Furthermore, immunohistochemistry was used to investigate E‑cadherin expression in pancreatic cancer tissues, and survival analysis and COX regression analysis were conducted. In pancreatic cancer cells under hypoxic, serum‑starved and TGF‑β‑induced microenvironments, E‑cadherin protein and mRNA levels were significantly decreased (P<0.05), while vimentin protein and mRNA expression levels were significantly increased (P<0.05). The results of immunohistochemistry showed that the protein level of E‑cadherin in pancreatic cancer tissues was positively correlated with overall survival (P<0.01). The results of Cox regression analysis showed that E‑cadherin was an independent prognostic factor in pancreatic cancer. In conclusion, E‑cadherin expression was significantly decreased by microenvironment changes, and this decrease induced EMT in pancreatic cancer cells. E‑cadherin is an independent prognostic marker in pancreatic cancer patients.
本研究旨在研究微环境变化对胰腺癌细胞上皮-间充质转化（EMT）的影响，并确定 E-钙黏蛋白表达与胰腺癌患者预后的相关性。我们建立了胰腺癌细胞缺氧、血清缺乏和 TGF-β诱导的微环境模型，通过 Western blot 分析和实时 PCR 研究 EMT 相关分子、E-钙黏蛋白和波形蛋白的 mRNA 和蛋白表达变化。此外，采用免疫组织化学方法检测胰腺癌组织中 E-钙黏蛋白的表达，并进行生存分析和 COX 回归分析。在缺氧、血清饥饿和 TGF-β诱导的微环境中的胰腺癌细胞中，E-钙黏蛋白蛋白和 mRNA 水平显著降低（P<0.05），而波形蛋白蛋白和 mRNA 表达水平显著升高（P<0.05）。免疫组织化学结果表明，胰腺癌组织中 E-钙黏蛋白的蛋白水平与总生存期呈正相关（P<0.01）。Cox 回归分析结果表明，E-钙黏蛋白是胰腺癌的独立预后因素。总之，微环境变化显著降低了 E-钙黏蛋白的表达，并诱导胰腺癌细胞发生 EMT。E-钙黏蛋白是胰腺癌患者的独立预后标志物。
