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Experimental cell research v.361 no.1, 2017년, pp.19 - 29   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Gastric cancer tissue-derived mesenchymal stem cells impact peripheral blood mononuclear cells via disruption of Treg/Th17 balance to promote gastric cancer progression

Wang, Mei (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Chen, Bin (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Sun, Xiao-Xian (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Zhao, Xiang-Dong (Zhenjiang Provincial Blood Center, Zhenjiang, Jiangsu, China ) ; Zhao, Yuan-Yuan (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Sun, Li (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Xu, Chang-Gen (Zhenjiang Provincial Blood Center, Zhenjiang, Jiangsu, China ) ; Shen, Bo (Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China ) ; Su, Zhao-Liang (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Xu, Wen-Rong (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ; Zhu, Wei (School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China ) ;
  • 초록  

    Abstract Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro . PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo . Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naIve CD4 + T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME. Highlights GC-MSCs educate PBMCs to promote gastric cancer progression. GC-MSCs disrupt the Treg/Th17 balance in PBMCs. GC-MSCs induce Treg cell differentiation and suppress Th17 cell proliferation.


  • 주제어

    Mesenchymal stem cells .   Peripheral blood mononuclear cells .   Treg .   Th17 .   Tumor microenvironment .   Gastric cancer.  

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