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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

Cellular & Molecular Immunology volume 12, pages 692–699 (2015)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (Nos. 31270971, 81072406 and 31100650), the China Postdoctoral Science Foundation (Nos. 2013M541922) and the Independent Innovation Foundation of Shandong University (No. 2012TS143). We would like to thank Professor Jian Li (Beth Israel Deaconess Medical Center, Harvard Medical School) for providing the RGC-32 overexpression vector and the RGC-32 antibody.

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  1. Dr X Qu, Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan 250012, China. E-mail: quxun@sdu.edu.cn

Authors and Affiliations

  1. Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, China

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

  2. Biotherapy Center, Qingdao Central Hospital, the Second Affiliated Hospital, Qingdao University Medical College, Qingdao, China

    Peng Zhao & Daiqing Gao

  3. Neurosurgery, Qilu Hospital of Shandong University, Jinan, China

    Xingang Li

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Zhao, P., Gao, D., Wang, Q. et al. 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. Cell Mol Immunol 12, 692–699 (2015). https://doi.org/10.1038/cmi.2014.108

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