Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages

Publication date: Available online 3 May 2018 Source:Pharmacological Research Author(s): Zhangting Yao, Jieqiong Zhang, Bo Zhang, Guikai Liang, Xi Chen, Fengqi Yao, Xiaqing Xu, Honghai Wu, Qiaojun He, Ling Ding, Bo Yang 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. Graphical abstract
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research