In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 8 ( 2018-08), p. 3825-3836
Abstract:
Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour‐associated macrophages ( TAM s) appeared to be implicated in metformin‐induced antitumour activities. However, how metformin inhibits TAM s‐induced tumour progression remains ill‐defined. Here, we report that metformin‐induced antitumour and anti‐angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells. By skewing TAM polarization from M2‐ to M1‐like phenotype, metformin inhibited both tumour growth and angiogenesis. Depletion of TAM s by clodronate liposomes eliminated M2‐ TAM s‐induced angiogenic promotion, while also abrogating M1‐ TAM s‐mediated anti‐angiogenesis, thus promoting angiogenesis in tumours from metformin treatment mice. Further in vitro experiments using TAM s‐conditioned medium and a coculture system were performed, which demonstrated an inhibitory effect of metformin on endothelial sprouting and tumour cell proliferation promoted by M2‐polarized RAW 264.7 macrophages. Based on these results, metformin‐induced inhibition of tumour growth and angiogenesis is greatly contributed by skewing of TAM s polarization in microenvironment, thus offering therapeutic opportunities for metformin in cancer treatment.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2076114-4
