Journal Article

Response gene to complement 32 (RGC-32) expression on M2-polarized and tumor-associated macrophages is M-CSF-dependent and enhanced by tumor-derived IL-4

Shao, Qianqian, Qu, Xun, Gao, Daiqing, Li, Xingang, Ji, Chunyan, Sun, Jintang, Li, Peng, Wang, Qingjie, Song, Bingfeng, Zhao, Peng

2015

Overview

Response gene to complement 32 (RGC-32) is a cell cycle regulator involved in the proliferation, differentiation and migration of cells and has also been implicated in angiogenesis. Here we show that RGC-32 expression in macrophages is induced by IL-4 and reduced by LPS, indicating a link between RGC-32 expression and M2 polarization. We demonstrated that the increased expression of RGC-32 is characteristic of alternatively activated macrophages, in which this protein suppresses the production of pro-inflammatory cytokine IL-6 and promotes the production of the anti-inflammatory mediator TGF-β. Consistent with in vitro data, tumor-associated macrophages (TAMs) express high levels of RGC-32, and this expression is induced by tumor-derived ascitic fluid in an M-CSF- and/or IL-4-dependent manner. Collectively, these results establish RGC-32 as a marker for M2 macrophage polarization and indicate that this protein is a potential target for cancer immunotherapy, targeting tumor-associated macrophages.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adenocarcinoma - genetics / Adenocarcinoma - immunology / Adenocarcinoma - pathology / Angiogenesis / Antibodies / Ascitic fluid / Ascitic Fluid - chemistry / Biomedical and Life Sciences / Biomedicine / Cancer immunotherapy / Cell cycle / Cell Cycle Proteins - genetics / Cell Cycle Proteins - immunology / Cell differentiation / Cell Differentiation - drug effects / Cell Line / Cell Movement - drug effects / Cell proliferation / Cell Proliferation - drug effects / Colonic Neoplasms - genetics / Colonic Neoplasms - immunology / Colonic Neoplasms - pathology / Gene Expression Regulation, Neoplastic / Humans / Immunology / Inflammation / Interleukin 4 / Interleukin 6 / Interleukin-4 - genetics / Interleukin-4 - immunology / Interleukin-6 - genetics / Interleukin-6 - immunology / Leukocyte migration / Leukocytes, Mononuclear - drug effects / Leukocytes, Mononuclear - immunology / Leukocytes, Mononuclear - pathology / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Macrophage Activation - drug effects / Macrophage colony-stimulating factor / Macrophage Colony-Stimulating Factor - genetics / Macrophage Colony-Stimulating Factor - immunology / Macrophages / Macrophages - drug effects / Macrophages - immunology / Macrophages - pathology / Medical Microbiology / Microbiology / Muscle Proteins - genetics / Muscle Proteins - immunology / Nerve Tissue Proteins - genetics / Nerve Tissue Proteins - immunology / Polarization / Primary Cell Culture / research-article / Retinal ganglion cells / Signal Transduction / Tetradecanoylphorbol Acetate - pharmacology / Transforming Growth Factor beta - genetics / Transforming Growth Factor beta - immunology / Tumors / Vaccine