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    陈义杨, 刘建文. 肥大细胞调控IDO诱导的肺癌细胞转移[J]. 华东理工大学学报(自然科学版), 2019, 45(3): 432-439. DOI: 10.14135/j.cnki.1006-3080.20180402001
    引用本文: 陈义杨, 刘建文. 肥大细胞调控IDO诱导的肺癌细胞转移[J]. 华东理工大学学报(自然科学版), 2019, 45(3): 432-439. DOI: 10.14135/j.cnki.1006-3080.20180402001
    CHEN Yiyang, LIU Jianwen. Inhibition of Mast Cells Against IDO-Induced Metastasis of Lung Carcinoma Cells[J]. Journal of East China University of Science and Technology, 2019, 45(3): 432-439. DOI: 10.14135/j.cnki.1006-3080.20180402001
    Citation: CHEN Yiyang, LIU Jianwen. Inhibition of Mast Cells Against IDO-Induced Metastasis of Lung Carcinoma Cells[J]. Journal of East China University of Science and Technology, 2019, 45(3): 432-439. DOI: 10.14135/j.cnki.1006-3080.20180402001

    肥大细胞调控IDO诱导的肺癌细胞转移

    Inhibition of Mast Cells Against IDO-Induced Metastasis of Lung Carcinoma Cells

    • 摘要: 建立了小鼠肥大细胞体外诱导体系。探究肥大细胞对肿瘤细胞侵袭转移能力的影响。Transwell迁移和侵袭实验检测了与肥大细胞共培养后的细胞2LL侵袭转移能力变化。实验结果表明:肥大细胞能够抑制IDO诱导的细胞2LL的侵袭转移能力。生物信息学分析发现基质金属蛋白酶抑制剂-1(TIMP1)能够抑制促肿瘤转移的基质金属蛋白酶-1(MMP1)、基质金属蛋白酶-2(MMP2)以及基质金属蛋白酶-9(MMP9)的表达。Western blot结果表明肥大细胞通过抑制STAT3磷酸化而减少IDO的表达;并通过TIMP1信号通路抑制MMP2、MMP9和VEGF的表达。这些结果表明肥大细胞通过抑制STAT3信号通路磷酸化调控IDO表达和抑制下游TIMP1、MMP2、MMP9信号通路抑制细胞2LL转移能力。

       

      Abstract: The aim of this study is to investigate IDO expression and metastasis ability of lung carcinoma cells after co-culturing with mast cells. Mast cells were obtained from C57BL/6 mice (aged 4—6 weeks), and a cellular phenotype analysis was performed by flow cytometry. IDO expression in lung carcinoma cells was detected by real-time PCR and western blotting. Transwell migration and invasion assays were used to assess the metastasis capacity of lung carcinoma cells. Moreover, the effects of culturing lung carcinoma cells with mast cells on the STAT3 and TIMP/MMP signaling pathways were determined by western blotting. Afterwards, metastatic-associated gene expression data were obtained from Gene Expression Omnibus database with 2 metastatic samples and 2 healthy samples. We subsequently analyzed differentially expressed genes (DEGs) in metastatic colonization using R software. IDO expression in lung carcinoma cells was attenuated after co-culturing with mast cells. The migration and invasion abilities of lung carcinoma cells in the co-culture system were decreased. The identified DEGs including 1 368 mRNAs were dysregulated in metastatic nodes. TIMP1 was down-regulated in metastatic nodes. The mechanisms by which mast cells restrain the metastasis behavior of lung carcinoma cell as well as the STAT3 signaling pathway, and limit MMP2/MMP9 expression by promoting TIMP1 expression. In conclusion, Mast cells restrain the expression of IDO in lung carcinoma cells by inhibiting STAT3 phosphorylation. The migration and invasion ability of lung carcinoma cells were restricted by the facilitated TIMP1 expression. Our study demonstrates a novel mechanism by which mast cells limit the lung carcinoma angiogenesis.

       

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