Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression
Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression
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白细胞介素 6 通过 STAT3 激活诱导 M2 巨噬细胞分化，与胃癌进展相关
DOI：
10.1007/s00262-017-2052-5
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发表时间：
2017-12-01
影响因子：
5.8
通讯作者：
Zhao, Yong-Liang
中科院分区：
文献类型：
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作者：
Fu, Xiao-Long;Duan, Wei;Zhao, Yong-Liang
白细胞介素6（IL-6）在肿瘤微环境中含量丰富，在肿瘤的发生、发展过程中起着重要作用。在我们的研究中，IL-6在36例胃癌（GC）患者的肿瘤组织中的表达显著高于非肿瘤组织。肿瘤组织中浸润的CD 163 + CD 206 +M2巨噬细胞数量明显多于非肿瘤组织中浸润的巨噬细胞数量。GC肿瘤中M2巨噬细胞的频率与IL-6的表达呈正相关。我们还发现IL-6可以通过激活STAT 3磷酸化诱导正常巨噬细胞分化为具有较高IL-10和TGF-β表达以及较低IL-12表达的M2巨噬细胞。因此，使用小干扰RNA敲低STAT 3降低了M2巨噬细胞相关细胞因子（IL-10和TGF-β）的表达。此外，IL-6诱导的M2巨噬细胞的上清液促进GC细胞增殖和迁移。此外，肿瘤中IL-6的产生和CD 163 + CD 206 +M2巨噬细胞浸润与疾病进展和GC患者生存率降低相关。总之，我们的数据表明，IL-6通过激活STAT 3磷酸化诱导M2巨噬细胞分化（IL-10高TGF-β高IL-12 p35低），并且IL-6诱导的M2巨噬细胞通过促进GC细胞增殖和迁移发挥促肿瘤功能。
Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163+CD206+M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. The frequencies of M2 macrophages were positively correlated with the IL-6 expression in GC tumors. We also found that IL-6 could induce normal macrophages to differentiate into M2 macrophages with higher IL-10 and TGF-β expression, and lower IL-12 expression, via activating STAT3 phosphorylation. Accordingly, knocking down STAT3 using small interfering RNA decreased the expression of M2 macrophages-related cytokines (IL-10 and TGF-β). Furthermore, supernatants from IL-6-induced M2 macrophages promote GC cell proliferation and migration. Moreover, IL-6 production and CD163+CD206+M2 macrophage infiltration in tumors were associated with disease progression and reduced GC patient survival. In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10highTGF-βhighIL-12p35low) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration.