Connective tissue growth factor is a positive regulator of epithelial-mesenchymal transition and promotes the adhesion with gastric cancer cells in human peritoneal mesothelial cells

Connective tissue growth factor is a positive regulator of epithelial-mesenchymal transition and promotes the adhesion with gastric cancer cells in human peritoneal mesothelial cells
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结缔组织生长因子是上皮间质转化的正调节因子,促进人腹膜间皮细胞与胃癌细胞的粘附

DOI:
10.1016/j.cyto.2012.09.013
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发表时间:
2013-01-01
期刊:
影响因子:
3.8
通讯作者:
Xu, Hui-Mian
Xu, Hui-Mian
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Cheng-Gang;Lv, Ling;Xu, Hui-Mian

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结缔组织生长因子(CTGF)参与人类癌症的发生和发展。上皮间质转化(EMT)在许多生物学过程中起着重要作用。本研究旨在探讨CTGF在腹膜间皮细胞EMT中的作用及CTGF对胃癌细胞与间皮细胞粘附的影响。将人腹膜间皮细胞(HPMCs)与TGF-β(1)或不同浓度的CTGF培养不同时间。通过形态学监测EMT过程。采用实时荧光定量RT-PCR和Western blot检测波形蛋白(vimentin)、α-SMA、E-cadherin和β-catenin的表达。RNA干扰用于实现CTGF的选择性和特异性敲低。我们证明,CTGF诱导间皮细胞EMT的剂量和时间依赖性的方式。将HPMC暴露于TGF-β(1),也经历与CTGF表达诱导相关的EMT。用CTGF siRNA转染能够部分逆转TGF-β处理后的EMT(1)。此外,诱导的HPMCs EMT与胃癌细胞与间皮细胞的粘附增加有关。这些结果表明,CTGF不仅是一个重要的介质,但在腹膜间皮细胞的EMT,从而促进胃癌细胞粘附到腹膜的有效激活剂。(C)2012爱思唯尔有限公司保留所有权利。
Connective tissue growth factor (CTGF) is involved in human cancer development and progression. Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes. In this study, we wished to investigate the role of CTGF in EMT of peritoneal mesothelial cells and the effects of CTGF on adhesion of gastric cancer cells to mesothelial cells. Human peritoneal mesothelial cells (HPMCs) were cultured with TGF-beta(1) or various concentrations of CTGF for different time. The EMT process was monitored by morphology. Real-time RT-PCR and Western blot were used to evaluate the expression of vimentin, alpha-SMA, E-cadherin and beta-catenin. RNA interference was used to achieve selective and specific knockdown of CTGF. We demonstrated that CTGF induced EMT of mesothelial cells in a dose- and time-dependent manner. HPMCs were exposed to TGF-beta(1), also underwent EMT which was associated with the induction of CTGF expression. Transfection with CTGF siRNA was able to reverse the EMT partially after treatment of TGF-beta(1). Moreover, the induced EMT of HPMCs was associated with an increased adhesion of gastric cancer cells to mesothelial cells. These findings suggest that CTGF is not only an important mediator but a potent activator of EMT in peritoneal mesothelial cells, which in turn promotes gastric cancer cell adhesion to peritoneum. (C) 2012 Elsevier Ltd. All rights reserved.