Activation of mesenchymal stem cells by macrophages promotes tumor progression through immune suppressive effects.
Activation of mesenchymal stem cells by macrophages promotes tumor progression through immune suppressive effects.
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巨噬细胞激活间充质干细胞通过免疫抑制作用促进肿瘤进展
DOI：
10.18632/oncotarget.8064
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发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Tian J
中科院分区：
文献类型：
--
作者：
Jia XH;Feng GW;Wang ZL;Du Y;Shen C;Hui H;Peng D;Li ZJ;Kong DL;Tian J
癌症的发展和进展与肿瘤相关巨噬细胞（TAM）有关。不同的TAM亚群在癌症中发挥保护作用或致病作用。已经描述了M1巨噬细胞在致癌作用中的保护作用，其激活抗肿瘤机制。相比之下，从实体瘤和转移瘤中分离的TAM具有抑制性M2样表型，这可以支持肿瘤进展的多个方面。目前，尚不清楚肿瘤相关基质中的巨噬细胞如何被劫持来支持肿瘤生长。间充质干细胞（MSC）与先天免疫系统的组分积极相互作用，并显示抗炎和促炎作用。在这里，我们测试了在M1巨噬细胞存在的情况下，MSC是否有利于肿瘤逃避免疫监视。我们发现经M1条件培养液培养的骨髓间充质干细胞（cMSCs）在体内促进肿瘤生长的能力大大增强。细胞因子/趋化因子的检查表明，cMSC获得了调节谱，其表达高水平的iNOS和MCP 1。与cMSC中MCP 1表达升高一致，cMSC的肿瘤促进作用依赖于MCP 1介导的巨噬细胞募集到肿瘤部位。此外，cMSCs分泌的IL-6还能促进TAM向M2样巨噬细胞的浸润。因此，当肿瘤微环境中的巨噬细胞转变为M1促炎型时，MSC将充当不良的传感器和开关器以加速肿瘤生长。
Cancer development and progression is linked to tumor-associated macrophages (TAMs). Distinct TAMs subsets perform either protective or pathogenic effects in cancer. A protective role in carcinogenesis has been described for M1 macrophages, which activate antitumor mechanisms. By comparison, TAMs isolated from solid and metastatic tumors have a suppressive M2-like phenotype, which could support multiple aspects of tumor progression. Currently, it has not been clearly understood how macrophages in tumor-associated stroma could be hijacked to support tumor growth. Mesenchymal stem cells (MSCs) actively interact with components of the innate immune system and display both anti-inflammatory and pro-inflammatory effects. Here, we tested whether MSCs could favor the tumor to escape from immunologic surveillance in the presence of M1 macrophages. We found that MSCs educated by M1 condition medium (cMSCs) possessed a greatly enhanced ability in promoting tumor growth in vivo. Examination of cytokines/chemokines showed that the cMSCs acquired a regulatory profile, which expressed high levels of iNOS and MCP1. Consistent with an elevated MCP1 expression in cMSCs, the tumor-promoting effect of the cMSCs depended on MCP1 mediated macrophage recruitment to tumor sites. Furthermore, IL-6 secreted by the cMSCs could polarize infiltrated TAMs into M2-like macrophages. Therefore, when macrophages changed into M1 pro-inflammation type in tumor microenvironment, the MSCs would act as poor sensors and switchers to accelerate tumor growth.