Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma

L Treps 1 S Edmond 2 E Harford-Wright 3, 1, 4 Em Galan-Moya 1 Anne Schmitt 1 A Azzi 1 A Citerne 1 N Bidère 1, 4, 3 D Ricard 5 Julie Gavard 1, 4, 3, *
* Corresponding author
4 Equipe 15 - SOAP - Signaling in Oncogenesis, Angiogenesis and Permeability
CHU Angers - Centre Hospitalier Universitaire d'Angers, Hôtel-Dieu de Nantes, Hôpital Laennec, CNRS - Centre National de la Recherche Scientifique : UMR6299, CRCNA - Centre de Recherche en Cancérologie/Nantes - Angers
Abstract : Glioblastoma are malignant highly vascularized brain tumours, which feature large oedema resulting from tumour-promoted vascular leakage. The pro-permeability factor Semaphorin3A (Sema3A) produced within glioblastoma has been linked to the loss of endothelial barrier integrity. Here, we report that extracellular vesicles (EVs) released by patient-derived glioblastoma cells disrupt the endothelial barrier. EVs expressed Sema3A at their surface, which accounted for in vitro elevation of brain endothelial permeability and in vivo vascular permeability, in both skin and brain vasculature. Blocking Sema3A or its receptor Neuropilin1 (NRP1) hampered EV-mediated permeability. In vivo models using ectopically and orthotopically xenografted mice revealed that Sema3A-containing EVs were efficiently detected in the blood stream. In keeping with this idea, sera from glioblastoma multiforme (GBM) patients also contain high levels of Sema3A carried in the EV fraction that enhanced vascular permeability, in a Sema3A/ NRP1-dependent manner. Our results suggest that EV-delivered Sema3A orchestrates loss of barrier integrity in glioblastoma and may be of interest for prognostic purposes.
Document type :
Journal articles
Complete list of metadatas

Cited literature [33 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01406334
Contributor : Elizabeth Bernardo <>
Submitted on : Thursday, December 1, 2016 - 9:44:03 AM
Last modification on : Thursday, April 11, 2019 - 4:02:56 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Citation

L Treps, S Edmond, E Harford-Wright, Em Galan-Moya, Anne Schmitt, et al.. Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma. Oncogene, Nature Publishing Group, 2016, 35, pp.2615 - 2623. ⟨10.1038/onc.2015.317⟩. ⟨inserm-01406334⟩

Share

Metrics

Record views

159