Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783549710891483136 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7312363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT azambujajulianah arginase1exosomesfromreprogrammedmacrophagespromoteglioblastomaprogression AT ludwignils arginase1exosomesfromreprogrammedmacrophagespromoteglioblastomaprogression AT yernenisaigopalakrishnas arginase1exosomesfromreprogrammedmacrophagespromoteglioblastomaprogression AT braganholelizandra arginase1exosomesfromreprogrammedmacrophagespromoteglioblastomaprogression AT whitesidetheresal arginase1exosomesfromreprogrammedmacrophagespromoteglioblastomaprogression |