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 (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-β1 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, α-SMA , E-cadherin and β-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-β1 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-β1. 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.
Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, and Department of Cell Biology, China Medical University, Shenyang 110001, Liaoning Province, China.
Cheng-Gang
CG
Jiang
Ling
L
Lv
Fu-Rong
FR
Liu
Zhen-Ning
ZN
Wang
Di
D
Na
Feng
F
Li
Jia-Bin
JB
Li
Zhe
Z
Sun
Hui-Mian
HM
Xu
D000199:Actins / Q000096:biosynthesis; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D010529:Peritoneal Cavity / Q000166:cytology; D010537:Peritoneum / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014746:Vimentin / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D051176:beta Catenin; D055513:Connective Tissue Growth Factor