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Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models
Inflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347707/ https://www.ncbi.nlm.nih.gov/pubmed/27756885 http://dx.doi.org/10.18632/oncotarget.12694 |
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author | Wolfe, Adam R. Trenton, Nicholaus J Debeb, Bisrat G. Larson, Richard Ruffell, Brian Chu, Khoi Hittelman, Walter Diehl, Michael Reuben, Jim M Ueno, Naoto T. Woodward, Wendy A. |
author_facet | Wolfe, Adam R. Trenton, Nicholaus J Debeb, Bisrat G. Larson, Richard Ruffell, Brian Chu, Khoi Hittelman, Walter Diehl, Michael Reuben, Jim M Ueno, Naoto T. Woodward, Wendy A. |
author_sort | Wolfe, Adam R. |
collection | PubMed |
description | Inflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-marrow derived mesenchymal stem cells (MSCs), and IBC cells (SUM 149 and MDA-IBC3). We used an in vivo model that reproduces the IBC phenotype by co-injecting IBC cells with MSCs into the mammary fat pad. Mice were then treated with a macrophage recruitment inhibitor, anti-CSF1. MSC and macrophages grown in co-culture produced higher levels of pro-tumor properties such as enhanced migration and elevated IL-6 secretion. IBC cells co-cultured with educated MSCs also displayed enhanced invasion and mammosphere formation and blocked by anti-IL-6 and statin treatment. The treatment of mice co-injected with IBC cells and MSCs with anti-CSF1 inhibited tumor associated macrophages and inhibited pSTAT3 expression in tumor cells. Anti-CSF1 treated mice also exhibited reduced tumor growth, skin invasion, and local recurrence. Herein we demonstrate reciprocal tumor interactions through IL-6 with cells found in the IBC microenvironment. Our results suggest IL-6 is a mediator of these tumor promoting influences and is important for the IBC induced migration of MSCs. |
format | Online Article Text |
id | pubmed-5347707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53477072017-03-31 Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models Wolfe, Adam R. Trenton, Nicholaus J Debeb, Bisrat G. Larson, Richard Ruffell, Brian Chu, Khoi Hittelman, Walter Diehl, Michael Reuben, Jim M Ueno, Naoto T. Woodward, Wendy A. Oncotarget Research Paper Inflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-marrow derived mesenchymal stem cells (MSCs), and IBC cells (SUM 149 and MDA-IBC3). We used an in vivo model that reproduces the IBC phenotype by co-injecting IBC cells with MSCs into the mammary fat pad. Mice were then treated with a macrophage recruitment inhibitor, anti-CSF1. MSC and macrophages grown in co-culture produced higher levels of pro-tumor properties such as enhanced migration and elevated IL-6 secretion. IBC cells co-cultured with educated MSCs also displayed enhanced invasion and mammosphere formation and blocked by anti-IL-6 and statin treatment. The treatment of mice co-injected with IBC cells and MSCs with anti-CSF1 inhibited tumor associated macrophages and inhibited pSTAT3 expression in tumor cells. Anti-CSF1 treated mice also exhibited reduced tumor growth, skin invasion, and local recurrence. Herein we demonstrate reciprocal tumor interactions through IL-6 with cells found in the IBC microenvironment. Our results suggest IL-6 is a mediator of these tumor promoting influences and is important for the IBC induced migration of MSCs. Impact Journals LLC 2016-10-15 /pmc/articles/PMC5347707/ /pubmed/27756885 http://dx.doi.org/10.18632/oncotarget.12694 Text en Copyright: © 2016 Wolfe et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wolfe, Adam R. Trenton, Nicholaus J Debeb, Bisrat G. Larson, Richard Ruffell, Brian Chu, Khoi Hittelman, Walter Diehl, Michael Reuben, Jim M Ueno, Naoto T. Woodward, Wendy A. Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models |
title | Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models |
title_full | Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models |
title_fullStr | Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models |
title_full_unstemmed | Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models |
title_short | Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models |
title_sort | mesenchymal stem cells and macrophages interact through il-6 to promote inflammatory breast cancer in pre-clinical models |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347707/ https://www.ncbi.nlm.nih.gov/pubmed/27756885 http://dx.doi.org/10.18632/oncotarget.12694 |
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