title: Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma.
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.
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Treps
authors.affiliation: Hopital d'Instruction des Armees du Val-de-Grace, Service de Neurologie, Paris Cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Edmond
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.|INSERM, U892, Nantes, France.|CNRS, UMR6299, Nantes, France.|University of Nantes, Nantes, France.
authors.forename: E
authors.initials: E
authors.lastname: Harford-Wright
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: E M
authors.initials: EM
authors.lastname: Galan-Moya
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Azzi
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Citerne
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.|INSERM, U892, Nantes, France.|CNRS, UMR6299, Nantes, France.|University of Nantes, Nantes, France.
authors.forename: N
authors.initials: N
authors.lastname: Bidère
authors.affiliation: Hopital d'Instruction des Armees du Val-de-Grace, Service de Neurologie, Paris Cedex, France.|CNRS, UMR8257, COGNAC G, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Ricard
authors.affiliation: CNRS, UMR8104, Paris, France.|Inserm, U1016, Paris, France.|Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.|INSERM, U892, Nantes, France.|CNRS, UMR6299, Nantes, France.|University of Nantes, Nantes, France.
authors.forename: J
authors.initials: J
authors.lastname: Gavard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D039942:Neuropilin-1 / Q000378:metabolism; D021381:Protein Transport; D040121:Semaphorin-3A / Q000378:metabolism*
chemical_list: D040121:Semaphorin-3A; D039942:Neuropilin-1