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Interstitial flow promotes macrophage polarization toward an M2 phenotype
Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behav...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232969/ https://www.ncbi.nlm.nih.gov/pubmed/29995595 http://dx.doi.org/10.1091/mbc.E18-03-0164 |
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author | Li, Ran Serrano, Jean Carlos Xing, Hao Lee, Tara A. Azizgolshani, Hesham Zaman, Muhammad Kamm, Roger D. |
author_facet | Li, Ran Serrano, Jean Carlos Xing, Hao Lee, Tara A. Azizgolshani, Hesham Zaman, Muhammad Kamm, Roger D. |
author_sort | Li, Ran |
collection | PubMed |
description | Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment. |
format | Online Article Text |
id | pubmed-6232969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62329692018-11-19 Interstitial flow promotes macrophage polarization toward an M2 phenotype Li, Ran Serrano, Jean Carlos Xing, Hao Lee, Tara A. Azizgolshani, Hesham Zaman, Muhammad Kamm, Roger D. Mol Biol Cell Articles Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment. The American Society for Cell Biology 2018-08-08 /pmc/articles/PMC6232969/ /pubmed/29995595 http://dx.doi.org/10.1091/mbc.E18-03-0164 Text en © 2018 Li et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Li, Ran Serrano, Jean Carlos Xing, Hao Lee, Tara A. Azizgolshani, Hesham Zaman, Muhammad Kamm, Roger D. Interstitial flow promotes macrophage polarization toward an M2 phenotype |
title | Interstitial flow promotes macrophage polarization toward an M2 phenotype |
title_full | Interstitial flow promotes macrophage polarization toward an M2 phenotype |
title_fullStr | Interstitial flow promotes macrophage polarization toward an M2 phenotype |
title_full_unstemmed | Interstitial flow promotes macrophage polarization toward an M2 phenotype |
title_short | Interstitial flow promotes macrophage polarization toward an M2 phenotype |
title_sort | interstitial flow promotes macrophage polarization toward an m2 phenotype |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232969/ https://www.ncbi.nlm.nih.gov/pubmed/29995595 http://dx.doi.org/10.1091/mbc.E18-03-0164 |
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