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...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-05-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/11/6/758 |
_version_ | 1797728506137804800 |
---|---|
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. |
first_indexed | 2024-03-12T11:15:00Z |
format | Article |
id | doaj.art-aadbf5f4952844f0bfbb70fd2efea244 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-12T11:15:00Z |
publishDate | 2019-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
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 |
work_keys_str_mv | AT ivanamanini semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT mariaelisabettaruaro semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT riccardosgarra semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT annabartolini semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT federicacaponnetto semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT tamaraius semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT miranskrap semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT carladiloreto semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT antoniopaolobeltrami semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT guidalbertomanfioletti semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment AT danielacesselli semaphorin7aonexosomesapromigratorysignalinthegliomamicroenvironment |