Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages.
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.
['Ding|Ling|L|', 'Liang|Guikai|G|', 'Yao|Zhangting|Z|', 'Zhang|Jieqiong|J|', 'Liu|Ruiyang|R|', 'Chen|Huihui|H|', 'Zhou|Yulu|Y|', 'Wu|Honghai|H|', 'Yang|Bo|B|', 'He|Qiaojun|Q|']
D000818:Animals D018827:Carcinoma, Lewis Lung D045744:Cell Line, Tumor D016764:Cell Polarity D008264:Macrophages D008687:Metformin D051379:Mice D008810:Mice, Inbred C57BL D009362:Neoplasm Metastasis D000067996:RAW 264.7 Cells D015398:Signal Transduction
metformin cancer metastasis AMPKα1 macrophage polarization