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70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

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Central nervous system tumour patients have elevated levels of circulating extracellular vesicles

Hirntumorpatienten besitzeneinen erhöhten Gehalt an zirkulierenden extrazellulären Vesikeln

Meeting Abstract

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  • presenting/speaker Franz Lennard Ricklefs - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Cecile Maire - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Katharina Kolbe - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Mareike Holz - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Rudolph Reimer - Heinrich-Pette-Institut, Hamburg, Deutschland
  • Markus Glatzel - Universitätsklinikum Hamburg-Eppendorf, Neuropathologie, Hamburg, Deutschland
  • E. Antonio Chiocca - Harvard Medical School, Dept. of Neurosurgery, Boston, MA, United States
  • Manfred Westphal - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Katrin Lamszus - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocV128

doi: 10.3205/19dgnc143, urn:nbn:de:0183-19dgnc1436

Veröffentlicht: 8. Mai 2019

© 2019 Ricklefs et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Objective: We previously demonstrated that extracellular vesicles (EV) from CNS tumors reflect the molecular subtype of the original tumor and mediate an exchange of pro-oncogenic signals. EV are commonly characterized by nanoparticle analysis (NTA), electron microscopy and tetraspanin markers, including CD9, CD81 and CD63. It is unclear, however, to what extent circulating tumor EVs are utilizable for diagnostic purposes and how their marker profile overlaps with EVs derived from other cell types. Aiming to define markers that allow distinction and enrichment of glioma EVs from patient blood, we utilized Imaging Flow Cytometry (IFC) to discriminate single EVs via multiple surface markers.

Methods: EVs were isolated from blood of patients suffering from glioblastoma (n=24), anaplastic astrocytoma (n=8), brain metastasis (n=7), meningioma (n=12), pituitary gland tumor (n=11), epilepsy (n=11) and from healthy controls (n=18) and analyzed by IFC, immunoblotting, electron microscopy and NTA. In addition, circulating EVs from PALM-GFP-GL261 and PALM-GFP-CT2A tumor-bearing mice (n=5) as well as from glioblastoma stem-like (GSC) cultures (n=4), neural stem cells (NSC), cerebral endothelial cells (cEC) and T-cells (n=4) were characterized.

Results: CNS tumor patients have significantly elevated levels of circulating EVs (P<0.001), as measured by NTA and IFC. In particular, the proportion of double positive CD9+/CD81+, CD9+/CD63+and CD63+/CD81+EVs is increased in glioblastoma patients (p=0.018) compared with healthy controls, while single positive CD9+or CD81+EVs are not. In accordance, cultured GSCs secrete increased levels of CD9+/CD81+EVs in vitro. In the two syngeneic murine PALM-GFP glioma models, only 0.1–0.01% of circulating plasma EVs were found to be derived from intracranial tumors, underlining the need to identify markers that can enrich tumor-specific EVs for molecular profiling.

Conclusion: Glioma patients display increased levels of circulating plasma EVs that can be profiled by IFC, which is a unique and novel technique that facilitates discrimination of different EV subpopulations.