CCR5 介导小鼠肝癌微环境中骨髓来源抑制性细胞的迁移
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(1.厦门医学院基础医学部福建厦门 361023; 2.机能与临床转化福建省高等学校重点实验室福建厦门 361023;3.厦门医学院呼吸疾病研究所福建厦门 361023)

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R-33

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CCR5 gene mediates migration of myeloid-derived suppressor cells in the mouse liver cancer microenvironment
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(1. Department of Basic Medicine, Xiamen Medical College, Xiamen 361023, China.2. Key Laboratory of Functional and Clinical Translational medicine, Fujian Province University, Xiamen 361023.3. Institute of Respiratory Diseases Xiamen Medical College, Xiamen 361023)

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    摘要:

    目的 探索CCR5 在小鼠肝癌微环境中MDSCs 迁移的作用?方法 建立原位肝癌小鼠模型,流式检测其骨髓来源抑制性细胞(myeloid-derived suppressor cells, MDSCs)水平?分选MDSCs,用CCR5 抑制剂100nmol/ L 预处理后观察小鼠肝癌细胞H22 条件培养基(tumor conditional medium, TCM)及CCR5 抑制剂对MDSCs 迁移的影响?最后在小鼠肝癌原位模型尾静脉注射DiR 标记的CCR5 抑制剂处理MDSCs,观察体内肝癌微环境下CCR5 抑制剂对MDSCs 的迁移影响?结果 在原位肝癌小鼠模型中,MDSCs 在骨髓?脾?肝中的水平与正常小鼠相比显著性升高;分选得到MDSCs 纯度可达94. 5%,且MDSCs 高表达CCR5?细胞迁移结果显示,CCR5 抑制剂能够抑制TCM 对MDSCs 的募集作用?小动物活体成像结果显示,MDSCs 经CCR5 抑制剂处理后其在体内向脾和肝迁移的作用也减弱?结论 在小鼠肝癌微环境中CCR5 介导MDSCs 在肿瘤微环境中迁移,抑制MDSCs 的CCR5 可能为肝癌的临床治疗提供新思路?

    Abstract:

    Objective To explore the role of CCR5 gene in the migration of myeloid-derived suppressor cells(MDSCs) into the mouse liver cancer microenvironment. Methods A mouse model of orthotopic liver cancer wasestablished and changes in the MDSCs were detected by flow cytometry. To observe the effect of mouse liver cancer cell H22(T-cell) conditional medium (TCM) on the migration of MDSCs, these cells were sorted and pretreated with 100 nmol/ LCCR5 inhibitor. Finally, DiR-labeled MDSCs were injected into the tail vein of mice with in situ hepatocarcinoma to observethe effect of the CCR5 inhibitor on the migration of MDSCs in vivo. Results The expression of MDSCs in bone marrow,spleen, and liver was significantly higher in the mouse model of orthotopic liver cancer than that in normal mice. The purityof MDSCs was 94. 5%, and MDSCs expressed CCR5. Cell migration result showed that CCR5 inhibitor reduced therecruitment of MDSCs by TCM. The in vivo imaging analysis showed that the ability of MDSCs to migrate to the spleen andliver in vivo was weakened after treatment with CCR5 inhibitor. Conclusions CCR5-mediated MDSCs accumulate in the mouse liver cancer microenvironment. Inhibition of CCR5 in MDSCs may provide a new idea for cancer treatment.

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许雅苹,郑晓辉,吴春,伊雪,黄黎月,王玉孝. CCR5 介导小鼠肝癌微环境中骨髓来源抑制性细胞的迁移[J].中国比较医学杂志,2019,29(7):29~35.

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  • 收稿日期:2019-01-22
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  • 在线发布日期: 2019-08-01
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