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, Gang Chen

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)21398-21409
Number of pages12
JournalOncotarget
Volume8
Issue number13
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
The authors would like to thank Drs. Maria Ramirez and Mary Williams at Boston University School of Medicine for providing E10 cells. We also want to thank Ms. Catherine E. Anthony of Markey Cancer Center at University of Kentucky for editing the manuscript. This work was supported by the American Cancer Society [RSG-11-116-01-CNE to G.C.], National Natural Science Foundation of China (No.31660325 to J.C.) and NCI Cancer Center Support Grant (P30 CA177558).

Keywords

  • Arsenic
  • Lung cancer
  • Macrophage
  • Transformation

ASJC Scopus subject areas

  • Oncology

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