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Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages

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 w...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722902/
https://www.ncbi.nlm.nih.gov/pubmed/36352257
http://dx.doi.org/10.1038/s12276-022-00886-x
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author 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
author_facet 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
author_sort Park, Seung-Ho
collection PubMed
description 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.
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spelling pubmed-97229022022-12-22 Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages 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 Exp Mol Med Article 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. Nature Publishing Group UK 2022-11-09 /pmc/articles/PMC9722902/ /pubmed/36352257 http://dx.doi.org/10.1038/s12276-022-00886-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
title Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
title_full Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
title_fullStr Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
title_full_unstemmed Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
title_short Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages
title_sort particulate matter promotes cancer metastasis through increased hbegf expression in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722902/
https://www.ncbi.nlm.nih.gov/pubmed/36352257
http://dx.doi.org/10.1038/s12276-022-00886-x
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