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Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression

Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resem...

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Autores principales: Azambuja, Juliana H., Ludwig, Nils, Yerneni, Saigopalakrishna S., Braganhol, Elizandra, Whiteside, Theresa L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312363/
https://www.ncbi.nlm.nih.gov/pubmed/32498400
http://dx.doi.org/10.3390/ijms21113990
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author Azambuja, Juliana H.
Ludwig, Nils
Yerneni, Saigopalakrishna S.
Braganhol, Elizandra
Whiteside, Theresa L.
author_facet Azambuja, Juliana H.
Ludwig, Nils
Yerneni, Saigopalakrishna S.
Braganhol, Elizandra
Whiteside, Theresa L.
author_sort Azambuja, Juliana H.
collection PubMed
description Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resembling the crosstalk between macrophages and glioblastoma cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) and M2 (mediate anti-inflammatory function) macrophages, converting M1 into TAMs and augmenting pro-tumor functions of M2 macrophages. In turn, these GBex-reprogrammed TAMs, produce exosomes decorated by immunosuppressive and tumor-growth promoting proteins. TAM-derived exosomes disseminate these proteins in the tumor microenvironment (TME) promoting tumor cell migration and proliferation. Mechanisms underlying the promotion of glioblastoma growth involved Arginase-1+ exosomes produced by the reprogrammed TAMs. A selective Arginase-1 inhibitor, nor-NOHA reversed growth-promoting effects of Arginase-1 carried by TAM-derived exosomes. The data suggest that GBex-reprogrammed Arginase-1+ TAMs emerge as a major source of exosomes promoting tumor growth and as a potential therapeutic target in glioblastoma.
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spelling pubmed-73123632020-06-26 Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression Azambuja, Juliana H. Ludwig, Nils Yerneni, Saigopalakrishna S. Braganhol, Elizandra Whiteside, Theresa L. Int J Mol Sci Article Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resembling the crosstalk between macrophages and glioblastoma cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) and M2 (mediate anti-inflammatory function) macrophages, converting M1 into TAMs and augmenting pro-tumor functions of M2 macrophages. In turn, these GBex-reprogrammed TAMs, produce exosomes decorated by immunosuppressive and tumor-growth promoting proteins. TAM-derived exosomes disseminate these proteins in the tumor microenvironment (TME) promoting tumor cell migration and proliferation. Mechanisms underlying the promotion of glioblastoma growth involved Arginase-1+ exosomes produced by the reprogrammed TAMs. A selective Arginase-1 inhibitor, nor-NOHA reversed growth-promoting effects of Arginase-1 carried by TAM-derived exosomes. The data suggest that GBex-reprogrammed Arginase-1+ TAMs emerge as a major source of exosomes promoting tumor growth and as a potential therapeutic target in glioblastoma. MDPI 2020-06-02 /pmc/articles/PMC7312363/ /pubmed/32498400 http://dx.doi.org/10.3390/ijms21113990 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Azambuja, Juliana H.
Ludwig, Nils
Yerneni, Saigopalakrishna S.
Braganhol, Elizandra
Whiteside, Theresa L.
Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression
title Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression
title_full Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression
title_fullStr Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression
title_full_unstemmed Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression
title_short Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression
title_sort arginase-1+ exosomes from reprogrammed macrophages promote glioblastoma progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312363/
https://www.ncbi.nlm.nih.gov/pubmed/32498400
http://dx.doi.org/10.3390/ijms21113990
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