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Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas
Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162015/ https://www.ncbi.nlm.nih.gov/pubmed/21901144 http://dx.doi.org/10.1371/journal.pone.0023902 |
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author | Gabrusiewicz, Konrad Ellert-Miklaszewska, Aleksandra Lipko, Maciej Sielska, Malgorzata Frankowska, Marta Kaminska, Bozena |
author_facet | Gabrusiewicz, Konrad Ellert-Miklaszewska, Aleksandra Lipko, Maciej Sielska, Malgorzata Frankowska, Marta Kaminska, Bozena |
author_sort | Gabrusiewicz, Konrad |
collection | PubMed |
description | Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases. Using immunofluorescence and flow cytometry, we demonstrate an early accumulation of activated microglia followed by accumulation of macrophages in experimental murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines and expression profiling of 28 genes in magnetically-sorted CD11b(+) cells from tumor tissues. Furthermore, we show that infiltration of implanted gliomas by amoeboid, Iba1-positive cells can be reduced by a systematically injected cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated levels of IL-10 and GM-CSF, increased expression of genes characteristic for the alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived CD11b(+) cells as well as enhanced angiogenesis and tumor growth were reduced in CsA-treated mice. Our findings define for the first time kinetics and biochemical characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the alternative activation of tumor-infiltrating macrophages significantly reduced tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro-invasive functions could be a novel therapeutic strategy in malignant gliomas. |
format | Online Article Text |
id | pubmed-3162015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31620152011-09-07 Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas Gabrusiewicz, Konrad Ellert-Miklaszewska, Aleksandra Lipko, Maciej Sielska, Malgorzata Frankowska, Marta Kaminska, Bozena PLoS One Research Article Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases. Using immunofluorescence and flow cytometry, we demonstrate an early accumulation of activated microglia followed by accumulation of macrophages in experimental murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines and expression profiling of 28 genes in magnetically-sorted CD11b(+) cells from tumor tissues. Furthermore, we show that infiltration of implanted gliomas by amoeboid, Iba1-positive cells can be reduced by a systematically injected cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated levels of IL-10 and GM-CSF, increased expression of genes characteristic for the alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived CD11b(+) cells as well as enhanced angiogenesis and tumor growth were reduced in CsA-treated mice. Our findings define for the first time kinetics and biochemical characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the alternative activation of tumor-infiltrating macrophages significantly reduced tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro-invasive functions could be a novel therapeutic strategy in malignant gliomas. Public Library of Science 2011-08-25 /pmc/articles/PMC3162015/ /pubmed/21901144 http://dx.doi.org/10.1371/journal.pone.0023902 Text en Gabrusiewicz et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Gabrusiewicz, Konrad Ellert-Miklaszewska, Aleksandra Lipko, Maciej Sielska, Malgorzata Frankowska, Marta Kaminska, Bozena Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas |
title | Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas |
title_full | Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas |
title_fullStr | Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas |
title_full_unstemmed | Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas |
title_short | Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas |
title_sort | characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162015/ https://www.ncbi.nlm.nih.gov/pubmed/21901144 http://dx.doi.org/10.1371/journal.pone.0023902 |
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