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

doi:10.18632/oncotarget.15232

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

Pharmacology and Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

23 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 language	English
Pages (from-to)	21398-21409
Number of pages	12
Journal	Oncotarget
Volume	8
Issue number	13
DOIs	https://doi.org/10.18632/oncotarget.15232
State	Published - 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).

Funding

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).

Funders	Funder number
American Cancer Society-Michigan Cancer Research Fund	RSG-11-116-01-CNE
American Cancer Society-Michigan Cancer Research Fund
National Childhood Cancer Registry – National Cancer Institute	P30CA177558
National Childhood Cancer Registry – National Cancer Institute
National Natural Science Foundation of China (NSFC)	31660325
National Natural Science Foundation of China (NSFC)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Arsenic
Lung cancer
Macrophage
Transformation

ASJC Scopus subject areas

Oncology

Access to Document

10.18632/oncotarget.15232

Cite this

@article{6b459f281e004b3bb22c2fd7faa4a774,

title = "M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells",

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.",

keywords = "Arsenic, Lung cancer, Macrophage, Transformation",

author = "Jiajun Cui and Wenhua Xu and Jian Chen and Hui Li and Lu Dai and Frank, \{Jacqueline A.\} and Shaojun Peng and Siying Wang and Gang Chen",

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).",

year = "2017",

doi = "10.18632/oncotarget.15232",

language = "English",

volume = "8",

pages = "21398--21409",

number = "13",

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TY - JOUR

T1 - M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells

AU - Cui, Jiajun

AU - Xu, Wenhua

AU - Chen, Jian

AU - Li, Hui

AU - Dai, Lu

AU - Frank, Jacqueline A.

AU - Peng, Shaojun

AU - Wang, Siying

AU - Chen, Gang

N1 - 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).

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Arsenic

KW - Lung cancer

KW - Macrophage

KW - Transformation

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AN - SCOPUS:85016391808

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VL - 8

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ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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