title: DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients.
abstract: Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs-apoptotic bodies, shedding microvesicles and exosomes-cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1G395A, an essential biomarker in the current management of human glioma.
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.|IMDEA Nanoscience, Madrid, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: García-Romero
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.|Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Carrión-Navarro
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.|Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Esteban-Rubio
authors.affiliation: Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lázaro-Ibáñez
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: María
authors.initials: M
authors.lastname: Peris-Celda
authors.affiliation: Clínica Universidad de Navarra, CIMA, Pamplona, Spain.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Alonso
authors.affiliation: Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Guzmán-De-Villoria
authors.affiliation: Servicio de Neurocirugía, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Carballal
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.
authors.forename: Ana Ortiz
authors.initials: AO
authors.lastname: de Mendivil
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: García-Duque
authors.affiliation: Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Escobedo-Lucea
authors.affiliation: Departamento de Neurocirugía, Hospital Universitario la Fe, Valencia, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Prat-Acín
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.|Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Belda-Iniesta
authors.affiliation: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.|IMDEA Nanoscience, Madrid, Spain.|Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Ayuso-Sacido
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000378:metabolism / Q000473:pathology; D005260:Female; D005910:Glioma / Q000097:blood* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged
chemical_list: D004273:DNA, Neoplasm
keywords: biomarkers; blood-brain barrier; brain tumors; extracellular vesicles