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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...

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Autores principales: Li, Ran, Serrano, Jean Carlos, Xing, Hao, Lee, Tara A., Azizgolshani, Hesham, Zaman, Muhammad, Kamm, Roger D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
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.
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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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