Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.
J Exp Clin Cancer Res. 2010 Oct 29;29(1):139. doi: 10.1186/1756-9966-29-139.
Peritoneal dissemination is one of the main causes of death in gastric cancer patients. Transforming growth factor-beta1 (TGF-β1), one of the most potent fibrotic stimuli for mesothelial cells, may play a key role in this processing. The purpose of this study is to elucidate the effects of TGF-β1 on regulation of gastric cancer adhesion to mesothelial cells.
Peritoneal tissues and peritoneal wash fluid were obtained for hematoxylin and eosin staining or ELISA to measure fibrosis and TGF-β1 levels, respectively. The peritoneal mesothelial cell line, HMrSV5, was used to determine the role of TGF-β1 in regulation of gastric cancer cell adhesion to mesothelial cells and expression of collagen, fibronectin, and Smad 2/3 by using adhesion assay, western blot, and RT-PCR.
The data showed that TGF-β1 treatment was able to induce collagen III and fibronectin expression in the mesothelial cells, which was associated with an increased adhesion ability of gastric cancer cells, but knockdown of minimal sites of cell binding domain of extracellular matrix can partially inhibit these effects.
Peritoneal fibrosis induced by TGF-β1 may provide a favorable environment for the dissemination of gastric cancer.
腹膜转移是胃癌患者死亡的主要原因之一。转化生长因子-β1(TGF-β1)是对间皮细胞最有效的纤维化刺激物之一,它可能在这一过程中发挥关键作用。本研究旨在阐明 TGF-β1 对胃癌细胞与间皮细胞黏附的调节作用。
采集腹膜组织和腹膜冲洗液,分别进行苏木精和伊红染色或 ELISA 以测量纤维化和 TGF-β1 水平。使用黏附试验、Western blot 和 RT-PCR,利用腹膜间皮细胞系 HMrSV5,确定 TGF-β1 在调节胃癌细胞与间皮细胞黏附以及胶原、纤维连接蛋白和 Smad 2/3 表达中的作用。
数据表明,TGF-β1 处理能够诱导间皮细胞中胶原 III 和纤维连接蛋白的表达,这与胃癌细胞黏附能力的增加有关,但细胞外基质最小结合域的敲低可以部分抑制这些作用。
TGF-β1 诱导的腹膜纤维化可能为胃癌的播散提供了有利的环境。