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Cell Res. 2013 Jul;23(7):898-914. doi: 10.1038/cr.2013.75. Epub 2013 Jun 11.

ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages.

Author information

1
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, RM1130, Bethesda, MD 20892, USA.

Abstract

Differentiation to different types of macrophages determines their distinct functions. Tumor-associated macrophages (TAMs) promote tumorigenesis owing to their proangiogenic and immune-suppressive functions similar to those of alternatively activated (M2) macrophages. We report that reactive oxygen species (ROS) production is critical for macrophage differentiation and that inhibition of superoxide (O(2-)) production specifically blocks the differentiation of M2 macrophages. We found that when monocytes are triggered to differentiate, O(2-) is generated and is needed for the biphasic ERK activation, which is critical for macrophage differentiation. We demonstrated that ROS elimination by butylated hydroxyanisole (BHA) and other ROS inhibitors blocks macrophage differentiation. However, the inhibitory effect of ROS elimination on macrophage differentiation is overcome when cells are polarized to classically activated (M1), but not M2, macrophages. More importantly, the continuous administration of the ROS inhibitor BHA efficiently blocked the occurrence of TAMs and markedly suppressed tumorigenesis in mouse cancer models. Targeting TAMs by blocking ROS can be a potentially effective method for cancer treatment.

PMID:
23752925
PMCID:
PMC3698641
DOI:
10.1038/cr.2013.75
[Indexed for MEDLINE]
Free PMC Article

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