Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
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DOI：
10.3389/fonc.2019.00855
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发表时间：
2019-09-10
影响因子：
4.7
通讯作者：
Wei, Xiawei
中科院分区：
文献类型：
--
作者：
Ma, Xuelei;Wang, Manni;Wei, Xiawei
目的：探讨骨髓来源的抑制细胞（MDSC）在肿瘤进展后的压力，手术切除和MDSC depletion.Summary背景数据的潜在治疗价值的作用：手术是最重要的治疗策略，在乳腺癌。最近的研究提供了证据表明，手术可能会促进癌症转移在某些情况下cancermetastasis.Methods：小鼠乳腺癌模型（管理的小鼠乳腺癌4T1细胞皮下）和手术的压力，用于比较免疫反应和生存结局。流式细胞术检测肿瘤组织及肺转移灶中CD11b和Gr1 MDSCs的表达。采用三色流式细胞术和酶联免疫吸附试验（ELISA）检测细胞因子水平。分离MDSC并与4T1细胞共培养以用免疫荧光鉴定任何形态学变化。结果：手术应激可使乳腺癌患者的生存率下降，导致MDSCs数量增加，并优先浸润肿瘤微环境，促进肿瘤转移。在体外和体内试验中，MDSC通过上调TGF-β 1、VEGF和IL-10诱导肿瘤细胞的上皮-间质转化（EMT）。结论：手术应激可降低小鼠的生存率。浸润的MDSC似乎诱导肿瘤细胞的EMT，并通过上调TGF-β 1、VEGF和IL-10水平增加转移。MDSC耗竭可能是一种有前途的治疗策略，以防止术后免疫逃避。
Objective: To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion.Summary Background Data: Surgery is the most important treatment strategy in breast cancer. Recent research has provided evidence that operations may promote cancer metastases under some circumstances.Methods: A mouse model of breast cancer (administration of the murine breast cancer 4T1 cells subcutaneously) and the stress of operation were used to compare immune responses and survival outcomes. Flow cytometry was performed to detect the expression of CD11b and Gr1 MDSCs in tumor tissues and lung metastases. Cytokine levels were detected with three-color flow cytometry and enzyme-linked immunosorbent assay (ELISA). MDSCs were isolated and co-cultured with 4T1 cells to identify any morphological change with immunofluorescence. The anti Gr-1 antibody was used to detect the function of the anti-Gr1 treatment in breast cancer.Results: The operative stress impaired the overall survival, leading to an increased number of MDSCs that preferentially infiltrated the tumor microenvironment and promoted tumor metastasis. In both in vitro and in vivo assays, MDSCs induced the epithelial-mesenchymal transition (EMT) of tumor cells through the up-regulation of TGF-beta1, VEGF, and IL-10. Furthermore, a treatment strategy of MDSC depletion was found to reduce pulmonary metastases after operations.Conclusions: The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations.