Role of transforming growth factor-β1 in epithelial-mesenchymal transition of mesothelial cells and its effect on peritoneal metastasis of gastric cancer
10.3760/cma.j.issn.1671-0274.2015.01.014
- VernacularTitle:转化生长因子β1对间皮细胞上皮-间质表型转化的调控及对胃癌腹膜转移的影响
- Author:
Zhidong LYU
1
;
Bin KONG
;
Xiangping LIU
;
Funian LI
;
Haibo WANG
;
Huimian XU
Author Information
1. 266003,青岛大学医学院附属医院乳腺外科
- Keywords:
Stomach neoplasms;
Epithelial-mesenchymal transition;
Mesothelial cells;
Transforming growth factor-beta1
- From:
Chinese Journal of Gastrointestinal Surgery
2015;(1):54-57
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the role of transforming growth factor-beta1 (TGF-β1) in epithelial-mesenchymal transition of mesothelial cells and peritoneal metastasis of gastric cancer. Methods HMrSV5 cells, a human peritoneal mesothelial cell line, were incubated with TGF-β1, and their morphological changes were observed by phase contrast microscopy. Expressions of α-smooth muscle actin (α-SMA), vimentin, cytokeratin, E-cadherin, phosphorylated-Smad2 and Smad2 were examined by Western blotting. After fibroblastic-like mesothelial cells were co-incubate with HSC-39 cells (gastric cancer cell line), the adhesion and invasion potential of HSC-39 were evaluated by adhesion and invasion assay in vitro. Results Few mesothelial cells converted to spindle fibroblast-like morphology for 24 h, and remarkable phenotypic changes were observed at 72 h of TGF-β1 activation. TGF-β1 could induce α-SMA and vimentin expression, and down-regulate cytokeratin and E-cadherin expression in mesothelial cells (P<0.05). TGF-β1 induced phosphorylation of Smad2 within 15 min of stimulation, reached a maximum at 30 min after treatment and remained high level during the experiment without affecting total Smad2 expression (P>0.05). The percentage of HSC-39 gastric cancer cells adhered were significantly increased as compared to the control. When the mesothelial cells were treated by TGF-β1 for 72 h, the increased adhesion percentage was (146 ±17)%(P<0.05). After fibroblastic-like mesothelial cells co-incubated with HSC-39 cells for 48 h , more cancer cells [(61.1 ±11.4) cells/view field] invaded the coated membrane as compared to the control group [(31.9±8.1) cells/view field] (P<0.05). Conclusion TGF-β1 can induce the transition of mesothelial cells into myofibroblasts and Smad2 signal pathway may play a role in this transition , which is associated with increased adhesion and invasiveness of gastric cancer cells , and provides favorable environment for the dissemination of gastric cancer.
