IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor.
IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor.
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DOI：
10.18632/oncotarget.24734
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发表时间：
2018-04-03
期刊：
影响因子：
--
通讯作者：
Xu N
中科院分区：
文献类型：
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作者：
Chen L;Wang S;Wang Y;Zhang W;Ma K;Hu C;Zhu H;Liang S;Liu M;Xu N
巨噬细胞在肿瘤发生中起着至关重要的作用，这取决于肿瘤微环境中发现的巨噬细胞的表型。迄今为止，肿瘤微环境如何影响巨噬细胞的表型尚未完全清楚。在这项研究中，我们构建了一个稳定过表达Src蛋白的NIH 3 T3/Src细胞系，发现该细胞系的条件培养基能够诱导原代骨髓源性巨噬细胞（BMDM）和Ana-1巨噬细胞向M2表型极化。进一步的研究表明，由NIH 3 T3/Src细胞产生的IL-6在M2极化中起关键作用。在C57 BL/6 J-ApcMin/+小鼠中结直肠癌的发展过程中，观察到结直肠组织的间质液中IL-6分泌增加。此外，与对照组相比，用IL-6敲除小鼠品系AOM-DSS处理的IL-6 tm 1 Kopf小鼠中的肿瘤发生被显著抑制，表明IL-6在促进肿瘤发生中的重要作用。我们的研究结果确定了负责促进肿瘤微环境中巨噬细胞向M2表型极化的靶分子和促炎细胞因子，这可能有助于设计结直肠癌的新治疗策略。
Macrophages play a crucial role in tumorigenesis depending upon the phenotype of macrophages found in tumor microenvironments. To date, how the tumor microenvironment affects the phenotypes of macrophages is not yet fully understood. In this study, we constructed a NIH3T3/Src cell line stably overexpresses the Src protein and found that conditioned medium from this cell line was able to induce polarization towards the M2 phenotype in primary bone marrow-derived macrophages (BMDM) and Ana-1 macrophages. Further investigation revealed that IL-6 produced by NIH3T3/Src cells plays a key role in M2 polarization. During the development of colorectal cancer in C57BL/6J-ApcMin/+ mice, increased IL-6 secretion in the interstitial fluid of the colorectal tissues was observed. Furthermore, tumorigenesis in IL-6tm1Kopf mice treated with AOM-DSS, an IL-6 knockout mouse strain, was significantly inhibited compared with the control group, suggesting the important role of IL-6 in promoting tumorigenicity. Our findings identify the target molecules and proinflammatory cytokines responsible for promoting polarization towards the M2 phenotype in macrophages present in tumor microenvironment, which may be useful for the design of novel therapeutic strategies for colorectal cancer.