Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages
Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages
复制标题
伊马替尼通过抑制巨噬细胞的 M2 样极化来预防肺癌转移
DOI：
10.1016/j.phrs.2018.05.002
复制
发表时间：
2018
影响因子：
9.3
通讯作者：
Yang Bo
中科院分区：
文献类型：
--
作者：
Yao Zhangting;Zhang Jieqiong;Zhang Bo;Liang Guikai;Chen Xi;Yao Fengqi;Xu Xiaqing;Wu Honghai;He Qiaojun;Ding Ling;Yang Bo
尽管 M2 样肿瘤相关巨噬细胞 (TAM) 由于其在促进肿瘤进展和转移中的作用而被认为是癌症治疗中的重要治疗靶点，但很少有化合物能够抑制 TAM 的 M2 样极化。在这里，我们发现伊马替尼在体外显着阻止 IL-13 或 IL-4 诱导的巨噬细胞 M2 样极化，细胞表面标志物 CD206 和 M2 样基因（包括 Arg1、Mgl2、Mrc1、CDH1 和 CCL2）的表达减少表明了这一点。此外，条件培养基促进的肺癌细胞从M2样巨噬细胞的迁移可以被伊马替尼抑制。从机制上讲，伊马替尼抑制 STAT6 磷酸化和核转位，导致巨噬细胞 M2 样极化停滞。此外，伊马替尼减少了Lewis肺癌的转移数量而不影响肿瘤生长。给予伊马替尼1周后，肿瘤和肺组织中M2样巨噬细胞的百分比均下降。综上所述，这些数据表明伊马替尼能够抑制巨噬细胞 M2 样极化，这在伊马替尼抑制 Lewis 肺癌转移中发挥着至关重要的作用。
Although M2-like tumor-associated macrophages (TAMs) have been considered as a vital therapeutic target in cancer therapy due to their role in promoting tumor progression and metastasis, very few compounds have been identified to inhibit M2-like polarization of TAMs. Here, we showed that Imatinib significantly prevented macrophage M2-like polarization induced by IL-13 or IL-4 in vitro, as illustrated by reduced expression of cell surface marker CD206 and M2-like genes, including Arg1, Mgl2, Mrc1, CDH1, and CCL2. Further, the migration of lung cancer cells promoted by the conditioned medium from M2-like macrophages could be restrained by Imatinib. Mechanistically, Imatinib inhibited STAT6 phosphorylation and nuclear translocation, resulting in the macrophage M2-like polarization arrest. Furthermore, Imatinib reduced the number of metastasis of Lewis lung cancer without affecting tumor growth. Both in tumor and lung tissues, the percentage of M2-like macrophages decreased after the administration of Imatinib for one week. Taken together, these data suggest that Imatinib is able to inhibit macrophage M2-like polarization, which plays a vital role in Imatinib suppressed metastasis of Lewis lung cancer.