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Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile

Immune system cells, including neutrophils, are recruited by the tumor microenvironment as a site of chronic inflammation and begin to favor tumor growth. Neutrophils present in the tumor site are called tumor-associated neutrophils (TAN) and can present two phenotypes: N1 (antitumor) or N2 (pro-tum...

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Autores principales: Amorim, Carolinne, Docasar, Clara Luisa, Guimarães-Bastos, Daniel, Frony, Ana Clara, Barja-Fidalgo, Christina, Renovato-Martins, Mariana, Moraes, João Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221190/
https://www.ncbi.nlm.nih.gov/pubmed/35741003
http://dx.doi.org/10.3390/cells11121875
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author Amorim, Carolinne
Docasar, Clara Luisa
Guimarães-Bastos, Daniel
Frony, Ana Clara
Barja-Fidalgo, Christina
Renovato-Martins, Mariana
Moraes, João Alfredo
author_facet Amorim, Carolinne
Docasar, Clara Luisa
Guimarães-Bastos, Daniel
Frony, Ana Clara
Barja-Fidalgo, Christina
Renovato-Martins, Mariana
Moraes, João Alfredo
author_sort Amorim, Carolinne
collection PubMed
description Immune system cells, including neutrophils, are recruited by the tumor microenvironment as a site of chronic inflammation and begin to favor tumor growth. Neutrophils present in the tumor site are called tumor-associated neutrophils (TAN) and can present two phenotypes: N1 (antitumor) or N2 (pro-tumor). Evidence shows the high capacity of immune system cells to interact with extracellular vesicles (Evs) released by tumor cells. Evs can modulate the phenotype of cells within the immune system, contributing to tumor development. Here, we investigated the role of MDA-MB-231-derived Evs upon the polarization of neutrophils towards an N2 phenotype and the underlying mechanisms. We observed that neutrophils treated with Evs released by MDA cells (MDA-Evs) had their half-life increased, increased their chemotactic capacity, and released higher levels of NETs and ROS than neutrophils treated with non-tumoral Evs. We also observed that neutrophils treated with MDA-Evs released increased IL-8, VEGF, MMP9, and increased expression of CD184, an N2-neutrophil marker. Finally, neutrophils treated with MDA-Evs increased tumor cell viability. Our results show that MDA-Evs induce an N2-like phenotype, and the blockage of phosphatidylserine by annexin-V may be an essential agent counter-regulating this effect.
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spelling pubmed-92211902022-06-24 Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile Amorim, Carolinne Docasar, Clara Luisa Guimarães-Bastos, Daniel Frony, Ana Clara Barja-Fidalgo, Christina Renovato-Martins, Mariana Moraes, João Alfredo Cells Article Immune system cells, including neutrophils, are recruited by the tumor microenvironment as a site of chronic inflammation and begin to favor tumor growth. Neutrophils present in the tumor site are called tumor-associated neutrophils (TAN) and can present two phenotypes: N1 (antitumor) or N2 (pro-tumor). Evidence shows the high capacity of immune system cells to interact with extracellular vesicles (Evs) released by tumor cells. Evs can modulate the phenotype of cells within the immune system, contributing to tumor development. Here, we investigated the role of MDA-MB-231-derived Evs upon the polarization of neutrophils towards an N2 phenotype and the underlying mechanisms. We observed that neutrophils treated with Evs released by MDA cells (MDA-Evs) had their half-life increased, increased their chemotactic capacity, and released higher levels of NETs and ROS than neutrophils treated with non-tumoral Evs. We also observed that neutrophils treated with MDA-Evs released increased IL-8, VEGF, MMP9, and increased expression of CD184, an N2-neutrophil marker. Finally, neutrophils treated with MDA-Evs increased tumor cell viability. Our results show that MDA-Evs induce an N2-like phenotype, and the blockage of phosphatidylserine by annexin-V may be an essential agent counter-regulating this effect. MDPI 2022-06-09 /pmc/articles/PMC9221190/ /pubmed/35741003 http://dx.doi.org/10.3390/cells11121875 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Amorim, Carolinne
Docasar, Clara Luisa
Guimarães-Bastos, Daniel
Frony, Ana Clara
Barja-Fidalgo, Christina
Renovato-Martins, Mariana
Moraes, João Alfredo
Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile
title Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile
title_full Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile
title_fullStr Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile
title_full_unstemmed Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile
title_short Extracellular Vesicles Derived from MDA-MB-231 Cells Trigger Neutrophils to a Pro-Tumor Profile
title_sort extracellular vesicles derived from mda-mb-231 cells trigger neutrophils to a pro-tumor profile
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221190/
https://www.ncbi.nlm.nih.gov/pubmed/35741003
http://dx.doi.org/10.3390/cells11121875
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