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Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment

Uveal melanoma (UM) is the most common primary intraocular tumor and often spreads to the liver. Intercellular communication though extracellular vesicles (EVs) plays an important role in several oncogenic processes, including metastasis, therapeutic resistance, and immune escape. This study examine...

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Autores principales: Piquet, Léo, Coutant, Kelly, Mitchell, Andrew, Ben Anes, Amel, Bollmann, Enola, Schoonjans, Nathan, Bérubé, Julie, Bordeleau, François, Brisson, Alain, Landreville, Solange
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736613/
https://www.ncbi.nlm.nih.gov/pubmed/36497088
http://dx.doi.org/10.3390/cells11233828
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author Piquet, Léo
Coutant, Kelly
Mitchell, Andrew
Ben Anes, Amel
Bollmann, Enola
Schoonjans, Nathan
Bérubé, Julie
Bordeleau, François
Brisson, Alain
Landreville, Solange
author_facet Piquet, Léo
Coutant, Kelly
Mitchell, Andrew
Ben Anes, Amel
Bollmann, Enola
Schoonjans, Nathan
Bérubé, Julie
Bordeleau, François
Brisson, Alain
Landreville, Solange
author_sort Piquet, Léo
collection PubMed
description Uveal melanoma (UM) is the most common primary intraocular tumor and often spreads to the liver. Intercellular communication though extracellular vesicles (EVs) plays an important role in several oncogenic processes, including metastasis, therapeutic resistance, and immune escape. This study examines how EVs released by UM cells modify stellate and endothelial cells in the tumor microenvironment. The surface markers, and the concentration and size of EVs derived from UM cells or choroidal melanocytes were characterized by high-resolution flow cytometry, electron microscopy, and Western blotting. The selective biodistribution of EVs was studied in mice by fluorescence imaging. The activation/contractility of stellate cells and the tubular organization of endothelial cells after exposure to melanomic EVs were determined by traction force microscopy, collagen gel contraction, or endothelial tube formation assays. We showed that large EVs from UM cells and healthy melanocytes are heterogenous in size, as well as their expression of phosphatidylserine, tetraspanins, and Tsg101. Melanomic EVs mainly accumulated in the liver and lungs of mice. Hepatic stellate cells with internalized melanomic EVs had increased contractility, whereas EV-treated endothelial cells developed more capillary-like networks. Our study demonstrates that the transfer of EVs from UM cells leads to a pro-fibrotic and pro-angiogenic phenotype in hepatic stellate and endothelial cells.
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spelling pubmed-97366132022-12-11 Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment Piquet, Léo Coutant, Kelly Mitchell, Andrew Ben Anes, Amel Bollmann, Enola Schoonjans, Nathan Bérubé, Julie Bordeleau, François Brisson, Alain Landreville, Solange Cells Article Uveal melanoma (UM) is the most common primary intraocular tumor and often spreads to the liver. Intercellular communication though extracellular vesicles (EVs) plays an important role in several oncogenic processes, including metastasis, therapeutic resistance, and immune escape. This study examines how EVs released by UM cells modify stellate and endothelial cells in the tumor microenvironment. The surface markers, and the concentration and size of EVs derived from UM cells or choroidal melanocytes were characterized by high-resolution flow cytometry, electron microscopy, and Western blotting. The selective biodistribution of EVs was studied in mice by fluorescence imaging. The activation/contractility of stellate cells and the tubular organization of endothelial cells after exposure to melanomic EVs were determined by traction force microscopy, collagen gel contraction, or endothelial tube formation assays. We showed that large EVs from UM cells and healthy melanocytes are heterogenous in size, as well as their expression of phosphatidylserine, tetraspanins, and Tsg101. Melanomic EVs mainly accumulated in the liver and lungs of mice. Hepatic stellate cells with internalized melanomic EVs had increased contractility, whereas EV-treated endothelial cells developed more capillary-like networks. Our study demonstrates that the transfer of EVs from UM cells leads to a pro-fibrotic and pro-angiogenic phenotype in hepatic stellate and endothelial cells. MDPI 2022-11-29 /pmc/articles/PMC9736613/ /pubmed/36497088 http://dx.doi.org/10.3390/cells11233828 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
Piquet, Léo
Coutant, Kelly
Mitchell, Andrew
Ben Anes, Amel
Bollmann, Enola
Schoonjans, Nathan
Bérubé, Julie
Bordeleau, François
Brisson, Alain
Landreville, Solange
Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
title Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
title_full Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
title_fullStr Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
title_full_unstemmed Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
title_short Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
title_sort extracellular vesicles from ocular melanoma have pro-fibrotic and pro-angiogenic properties on the tumor microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736613/
https://www.ncbi.nlm.nih.gov/pubmed/36497088
http://dx.doi.org/10.3390/cells11233828
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