Open AccessMetformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages
Author(s) -
Ling Ding,
Guikai Liang,
Zhangting Yao,
Jieqiong Zhang,
Ruiyang Liu,
Huihui Chen,
Yulu Zhou,
Honghai Wu,
Bo Yang,
Qiaojun He
Publication year - 2015
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.5541
Subject(s) - metformin , macrophage polarization , ampk , cancer research , metastasis , medicine , gene silencing , m2 macrophage , cancer cell , cancer , macrophage , endocrinology , chemistry , kinase , biology , protein kinase a , microbiology and biotechnology , diabetes mellitus , in vitro , biochemistry , gene
Accumulated evidence suggests that M2-like polarized tumor associated macrophages (TAMs) plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-like TAMs as an appealing target for therapy intervention. Here we found that metformin significantly suppressed IL-13 induced M2-like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-like macrophages promoted migration of cancer cells and endothelial cells. Metformin triggered AMPKα1 activation in macrophage and silencing of AMPKα1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization. Administration of AICAR, another activator of AMPK, also blocked the M2-like polarization of macrophages. Metformin greatly reduced the number of metastases of Lewis lung cancer without affecting tumor growth. In tumor tissues, the percentage of M2-like macrophage was decreased and the area of pericyte-coated vessels was increased. Further, the anti-metastatic effect of metformin was abolished when the animals were treated with macrophages eliminating agent clodronate liposome. These findings suggest that metformin is able to block the M2-like polarization of macrophages partially through AMPKα1, which plays an important role in metformin inhibited metastasis of Lewis lung cancer.