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

Cancers

Guidalberto Manfioletti¹  Riccardo Sgarra¹  Anna Bartolini²  Ivana Manini²  Daniela Cesselli²  AntonioPaolo Beltrami²  Federica Caponnetto²  Carla Di Loreto²  MariaElisabetta Ruaro²  Tamara Ius³  Miran Skrap³ 

[1] Department of Life Sciences, University of Trieste, Via Giorgieri 5, 34127 Trieste, Italy;Department of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy;Department of Neurosurgery, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy;

关键词: glioblastoma microenvironment;    exosomes;    Semaphorin 7A;    integrin β1/FAK signalling;    motility;   

DOI  :  10.3390/cancers11060758

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown