Research Papers:

M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells

Jiajun Cui _, Wenhua Xu, Jian Chen, Hui Li, Lu Dai, Jacqueline A. Frank, Shaojun Peng, Siying Wang and Gang Chen

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Oncotarget. 2017; 8:21398-21409. https://doi.org/10.18632/oncotarget.15232

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Jiajun Cui1,2,*, Wenhua Xu2,3,*, Jian Chen4,*, Hui Li2, Lu Dai5, Jacqueline A. Frank2, Shaojun Peng1, Siying Wang6, Gang Chen2

1Department of Biochemistry, Medical College of Yichun University, Yichun, Jiangxi 336000, China

2Department Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, USA

3Department of Neurology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, China

4Department of Ultrasound, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361001, China

5Department of Toxicology & Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA

6Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China

*These authors have contributed equally to this work

Correspondence to:

Jiajun Cui, email: [email protected]

Gang Chen, email: [email protected]

Keywords: macrophage, lung cancer, arsenic, transformation

Received: July 13, 2016    Accepted: January 16, 2017    Published: February 09, 2017


The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages.

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