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

Autor: Piquet L; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada.; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada., Coutant K; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada.; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada., Mitchell A; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada., Ben Anes A; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada., Bollmann E; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada.; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada., Schoonjans N; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada., Bérubé J; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada., Bordeleau F; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada.; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada., Brisson A; UMR-CBMN, CNRS-Université de Bordeaux-IPB, 33600 Pessac, France., Landreville S; Faculté de Médecine, Université Laval, Quebec City, QC G1V 0A6, Canada.; Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada.; Centre de Recherche sur le Cancer de l'Université Laval, Quebec City, QC G1R 3S3, Canada.; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Nov 29; Vol. 11 (23). Date of Electronic Publication: 2022 Nov 29.
DOI: 10.3390/cells11233828
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje