Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages

Cited 6 time in scopus
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Title
Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
Author(s)
Seung-Ho Park; Sung Jin Yoon; Song Choi; Jaeeun Jung; Jun Young Park; Young-Ho ParkJinho SeoJung Woon LeeMoo-Seung LeeSeon-Jin LeeMi-Young SonYoung Lai Cho; Jang Seong Kim; H J Lee; Jinyoung JeongDae Soo KimYoung-Jun Park
Bibliographic Citation
Experimental and Molecular Medicine, vol. 54, no. 11, pp. 1901-1912
Publication Year
2022
Abstract
Although many cohort studies have reported that long-term exposure to particulate matter (PM) can cause lung cancer, the molecular mechanisms underlying the PM-induced increase in cancer metastasis remain unclear. To determine whether PM contributes to cancer metastasis, cancer cells were cultured with conditioned medium from PM-treated THP1 cells, and the migration ability of the treated cancer cells was assessed. The key molecules involved were identified using RNA-seq analysis. In addition, metastatic ability was analyzed in vivo by injection of cancer cells into the tail vein and intratracheal injection of PM into the lungs of C57BL/6 mice. We found that PM enhances the expression of heparin-binding EGF-like growth factor (HBEGF) in macrophages, which induces epithelial-to-mesenchymal transition (EMT) in cancer cells, thereby increasing metastasis. Macrophage stimulation by PM results in activation and subsequent nuclear translocation of the aryl hydrocarbon receptor and upregulation of HBEGF. Secreted HBEGF activates EGFR on the cancer cell surface to induce EMT, resulting in increased migration and invasion in vitro and increased metastasis in vivo. Therefore, our study reveals a critical PM-macrophage-cancer cell signaling axis mediating EMT and metastasis and provides an effective therapeutic approach for PM-induced malignancy.
ISSN
1226-3613
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s12276-022-00886-x
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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