胃癌腹膜転移側の宿主細胞である腹膜中皮細胞(HPMC)において、TGF-β1や胃癌細胞との共培養によるEMT(上皮間葉転換）誘導を証明した。またマウス皮下腫瘍モデルを用い、胃癌細胞とHPMCの共投与は腫瘍増殖能や間質線維化の増生に促進的に作用する事を示した。さらにBRM製剤であるPSKは非免疫学的機序である抗TGFβ作用によって、これらのEMT誘導に伴う癌間質の線維化を抑制する事を証明した。
In this study, we evaluated the mechanism of EMT of Human PeritonealMesothelial Cell(HPMC) in in peritoneal environment of gastric cancer. We also investigated the inhibitory effect of PSK on the TGF/Smad signalling pathway and TGFb induced EMT in human HPMCs and gastric cancer cells. In vitro, TGFb increased the expression of E cadherin and decreased the expression of mesenchymal markers in HPMCs and which was suppressed by PSK. PSK suppressed TGFb induced phosphorylation of Smad2 in HPMCs in western blot analysis.In mouse subctaneous xenograft models, PSK inhibited the tumor fibrosis induced by co-inoculation of gastric cancer cells and HPMCs. PSK might have the potential to reduce TGFb induced activation of HPMCs in the peritoneal microenvironment of gastric cancer.
胃癌腹膜播種の微小環境における上皮間葉転換の解明と治療標的の意義
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ME-PR-KINOSHITA-J-kaken 2014-4p.pdf
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