Oncotarget

Research Papers:

DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients

Noemí García-Romero, Josefa Carrión-Navarro, Susana Esteban-Rubio, Elisa Lázaro-Ibáñez, María Peris-Celda, Marta M. Alonso, Juan Guzmán-De-Villoria, Carlos Fernández-Carballal, Ana Ortiz de Mendivil, Sara García-Duque, Carmen Escobedo-Lucea, Ricardo Prat-Acín, Cristóbal Belda-Iniesta and Angel Ayuso-Sacido _

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Oncotarget. 2017; 8:1416-1428. https://doi.org/10.18632/oncotarget.13635

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Abstract

Noemí García-Romero1,2,*, Josefa Carrión-Navarro1,3,*, Susana Esteban-Rubio1,3,*, Elisa Lázaro-Ibáñez4, María Peris-Celda5, Marta M. Alonso6, Juan Guzmán-De-Villoria7, Carlos Fernández-Carballal8, Ana Ortiz de Mendivil1, Sara García-Duque1, Carmen Escobedo-Lucea4, Ricardo Prat-Acín9, Cristóbal Belda-Iniesta1,3, Angel Ayuso-Sacido1,2,3

1Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain

2IMDEA Nanoscience, Madrid, Spain

3Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain

4Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

5Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

6Clínica Universidad de Navarra, CIMA, Pamplona, Spain

7Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain

8Servicio de Neurocirugía, Hospital General Universitario Gregorio Marañón, Madrid, Spain

9Departamento de Neurocirugía, Hospital Universitario la Fe, Valencia, Spain

*These authors have contributed equally to this work

Correspondence to:

Angel Ayuso-Sacido, email: [email protected]

Keywords: extracellular vesicles, brain tumors, blood-brain barrier, biomarkers

Received: September 20, 2016    Accepted: November 07, 2016    Published: November 26, 2016

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


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