DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients
García-Romero N (1,2), Carrión-Navarro J (1,3), Esteban-Rubio S (1,3), Lázaro-Ibáñez E (4), Peris-Celda M (5), Alonso MM (6), Guzmán-De-Villoria J (7), Fernández-Carballal C (8), Ortiz de Mendivil A (1), García-Duque S (1), Escobedo-Lucea C (4), Prat-Acín R (9), Belda-Iniesta C (1,3), Ayuso-Sacido A (1,2,3).
(1) Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.
(2) IMDEA Nanoscience, Madrid, Spain.
(3) Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain.
(4) Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
(5) Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
(6) Clínica Universidad de Navarra, CIMA, Pamplona, Spain.
(7) Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
(8) Servicio de Neurocirugía, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
(9) Departamento de Neurocirugía, Hospital Universitario la Fe, Valencia, Spain.
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.
CITATION Oncotarget. 2016 Nov 26. doi: 10.18632/oncotarget.13635