Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages

• Published in: Experimental & molecular medicine 2022-11, Vol.54 (11), p.1901-1912
• Main Authors: Park, Seung-Ho, Yoon, Sung-Jin, Choi, Song, Jung, Jaeeun, Park, Jun-Young, Park, Young-Ho, Seo, Jinho, Lee, Jungwoon, Lee, Moo-Seung, Lee, Seon-Jin, Son, Mi-Young, Cho, Young-Lai, Kim, Jang-Seong, Lee, Hyo Jin, Jeong, Jinyoung, Kim, Dae-Soo, Park, Young-Jun
• Format: Article
• Language: English
• Subjects: 13/1; 13/21; 13/89; 13/95; 631/250/2504/342; 631/67/322; 64/60; Animals; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Line, Tumor; Cell signaling; Cell surface; Epithelial-Mesenchymal Transition; Growth factors; Heparin; Heparin-binding EGF-like Growth Factor - metabolism; Heparin-binding epidermal growth factor-like growth factor; Inflammation; Inhalation; Leukocyte migration; Lung cancer; Macrophages; Macrophages - metabolism; Malignancy; Medical Biochemistry; Mesenchyme; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Molecular Medicine; Molecular modelling; Neoplasm Metastasis; Nuclear transport; Particulate matter; Particulate Matter - adverse effects; Pollutants; Stem Cells; Trachea; Tumors
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-022-00886-x

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. Cancer: Particulate matter pollutants promote progression The inhalation of tiny particles known as particulate matter (PM) from polluted air induces an inflammatory response in the lungs that may contribute to tumor metastasis. PM contributes to a host of respiratory problems including lung cancer, and many of these toxic effects are thought to arise from chemical signals released by immune cells upon exposure to these pollutants. Seung-Ho Park at the Korea Research Institute of Bioscience and Biotechnology, Daejon, South Koread, and coworkers have determined that immune cells exposed to PM secrete HBEGF, member of the EGF family of growth factors, which causes cultured cancer cells to transition into a more invasive, metastatic state. They observed a similar process in mice injected with cancer cells, where exposure to PM resulted in elevated HBEGF production and increased numbers of metastatic tumors.