Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment

Exosomes are one of the most important mediators of the cross talk occurring between glioma stem cells (GSCs) and the surrounding microenvironment. We have previously shown that exosomes released by patient-derived glioma-associated stem cells (GASC) are able to increase, in vitro, the aggressivenes...

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Main Authors: Ivana Manini, Maria Elisabetta Ruaro, Riccardo Sgarra, Anna Bartolini, Federica Caponnetto, Tamara Ius, Miran Skrap, Carla Di Loreto, Antonio Paolo Beltrami, Guidalberto Manfioletti, Daniela Cesselli
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/11/6/758
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author Ivana Manini
Maria Elisabetta Ruaro
Riccardo Sgarra
Anna Bartolini
Federica Caponnetto
Tamara Ius
Miran Skrap
Carla Di Loreto
Antonio Paolo Beltrami
Guidalberto Manfioletti
Daniela Cesselli
author_facet Ivana Manini
Maria Elisabetta Ruaro
Riccardo Sgarra
Anna Bartolini
Federica Caponnetto
Tamara Ius
Miran Skrap
Carla Di Loreto
Antonio Paolo Beltrami
Guidalberto Manfioletti
Daniela Cesselli
author_sort Ivana Manini
collection DOAJ
description Exosomes are one of the most important mediators of the cross talk occurring between glioma stem cells (GSCs) and the surrounding microenvironment. We have previously shown that exosomes released by patient-derived glioma-associated stem cells (GASC) are able to increase, in vitro, the aggressiveness of both GSC and glioblastoma cell lines. To understand which molecules are responsible for this tumour-supporting function, we performed a descriptive proteomic analysis of GASC-exosomes and identified, among the others, Semaphorin7A (SEMA7A). SEMA7A was described as a promigratory cue in physiological and pathological conditions, and we hypothesised that it could modulate GSC migratory properties. Here, we described that SEMA7A is exposed on GASC-exosomes’ surface and signals to GSC through Integrin β1. This interaction activates focal adhesion kinase into GSC and increases their motility, in our patient-based in vitro model. Our findings suggest SEMA7A-β1-integrin as a new target to disrupt the communication between GSCs and the supporting microenvironment.
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spelling doaj.art-aadbf5f4952844f0bfbb70fd2efea2442023-09-02T02:19:08ZengMDPI AGCancers2072-66942019-05-0111675810.3390/cancers11060758cancers11060758Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma MicroenvironmentIvana Manini0Maria Elisabetta Ruaro1Riccardo Sgarra2Anna Bartolini3Federica Caponnetto4Tamara Ius5Miran Skrap6Carla Di Loreto7Antonio Paolo Beltrami8Guidalberto Manfioletti9Daniela Cesselli10Department of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Life Sciences, University of Trieste, Via Giorgieri 5, 34127 Trieste, ItalyDepartment of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Neurosurgery, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Neurosurgery, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Life Sciences, University of Trieste, Via Giorgieri 5, 34127 Trieste, ItalyDepartment of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, ItalyExosomes are one of the most important mediators of the cross talk occurring between glioma stem cells (GSCs) and the surrounding microenvironment. We have previously shown that exosomes released by patient-derived glioma-associated stem cells (GASC) are able to increase, in vitro, the aggressiveness of both GSC and glioblastoma cell lines. To understand which molecules are responsible for this tumour-supporting function, we performed a descriptive proteomic analysis of GASC-exosomes and identified, among the others, Semaphorin7A (SEMA7A). SEMA7A was described as a promigratory cue in physiological and pathological conditions, and we hypothesised that it could modulate GSC migratory properties. Here, we described that SEMA7A is exposed on GASC-exosomes’ surface and signals to GSC through Integrin β1. This interaction activates focal adhesion kinase into GSC and increases their motility, in our patient-based in vitro model. Our findings suggest SEMA7A-β1-integrin as a new target to disrupt the communication between GSCs and the supporting microenvironment.https://www.mdpi.com/2072-6694/11/6/758glioblastoma microenvironmentexosomesSemaphorin 7Aintegrin β1/FAK signallingmotility
spellingShingle Ivana Manini
Maria Elisabetta Ruaro
Riccardo Sgarra
Anna Bartolini
Federica Caponnetto
Tamara Ius
Miran Skrap
Carla Di Loreto
Antonio Paolo Beltrami
Guidalberto Manfioletti
Daniela Cesselli
Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment
Cancers
glioblastoma microenvironment
exosomes
Semaphorin 7A
integrin β1/FAK signalling
motility
title Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment
title_full Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment
title_fullStr Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment
title_full_unstemmed Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment
title_short Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment
title_sort semaphorin 7a on exosomes a promigratory signal in the glioma microenvironment
topic glioblastoma microenvironment
exosomes
Semaphorin 7A
integrin β1/FAK signalling
motility
url https://www.mdpi.com/2072-6694/11/6/758
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