Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion

Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural...

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Autores principales:	Joman Javadi, André Görgens, Hanna Vanky, Dhanu Gupta, Anders Hjerpe, Samir EL-Andaloussi, Daniel Hagey, Katalin Dobra
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	malignant pleural mesothelioma pleural effusion extracellular vesicles biomarkers Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/26a0dd6081b64bd49f4f4167d2a340ad
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spelling	oai:doaj.org-article:26a0dd6081b64bd49f4f4167d2a340ad2021-11-25T16:52:44ZDiagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion10.3390/biom111116062218-273Xhttps://doaj.org/article/26a0dd6081b64bd49f4f4167d2a340ad2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1606https://doaj.org/toc/2218-273XExtracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (<i>n</i> = 9), benign (<i>n</i> = 6), and AD (<i>n</i> = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.Joman JavadiAndré GörgensHanna VankyDhanu GuptaAnders HjerpeSamir EL-AndaloussiDaniel HageyKatalin DobraMDPI AGarticlemalignant pleural mesotheliomapleural effusionextracellular vesiclesbiomarkersMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1606, p 1606 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	malignant pleural mesothelioma pleural effusion extracellular vesicles biomarkers Microbiology QR1-502
spellingShingle	malignant pleural mesothelioma pleural effusion extracellular vesicles biomarkers Microbiology QR1-502 Joman Javadi André Görgens Hanna Vanky Dhanu Gupta Anders Hjerpe Samir EL-Andaloussi Daniel Hagey Katalin Dobra Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion
description	Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (<i>n</i> = 9), benign (<i>n</i> = 6), and AD (<i>n</i> = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.
format	article
author	Joman Javadi André Görgens Hanna Vanky Dhanu Gupta Anders Hjerpe Samir EL-Andaloussi Daniel Hagey Katalin Dobra
author_facet	Joman Javadi André Görgens Hanna Vanky Dhanu Gupta Anders Hjerpe Samir EL-Andaloussi Daniel Hagey Katalin Dobra
author_sort	Joman Javadi
title	Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion
title_short	Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion
title_full	Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion
title_fullStr	Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion
title_full_unstemmed	Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion
title_sort	diagnostic and prognostic utility of the extracellular vesicles subpopulations present in pleural effusion
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/26a0dd6081b64bd49f4f4167d2a340ad
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Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion

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