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72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

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Longitudinal molecular and functional stability of a glioblastoma spheroid cultures supports their utility as reproducible in vitro models

Molekulare und funktionelle Stabilität von Langzeit Glioblastom-Sphäroidkulturen unterstützten ihre Nützlichkeit als reproduzierbare In-vitro-Modelle

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  • presenting/speaker Ann-Christin Nickel - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Daniel Picard - University Hospital Düsseldorf, Pediatric Oncology, Düsseldorf, Deutschland; German Cancer Consortium (DKTK), Essen/Düsseldorf, Deutschland
  • Marietta Wolters - University Hospital Düsseldorf, Neuropathology, Düsseldorf, Deutschland
  • Kerstin Kaulich - University Hospital Düsseldorf, Neuropathology, Düsseldorf, Deutschland
  • Sajjad Muhammad - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Guido Reifenberger - University Hospital Düsseldorf, Neuropathology, Düsseldorf, Deutschland
  • Daniel Hänggi - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Maria Stella Carro - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland; Faculty of Medicine Albert-Ludwig’s University, Department of Neurosurgery, Freiburg, Deutschland
  • Marc Remke - University Hospital Düsseldorf, Pediatric Oncology, Düsseldorf, Deutschland; German Cancer Consortium (DKTK), Essen/Düsseldorf, Deutschland
  • presenting/speaker Ulf Dietrich Kahlert - University Hospital Düsseldorf, Pediatric Oncology, Düsseldorf, Deutschland; German Cancer Consortium (DKTK), Essen/Düsseldorf, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocP138

doi: 10.3205/21dgnc426, urn:nbn:de:0183-21dgnc4267

Published: June 4, 2021

© 2021 Nickel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Reproducible and clinically relevant in vitro drug testing of gliomas depends on appropriate cell models. Glioma stem-like cell-based 3D cultures emerged as an alternative to monolayer cell lines as 3D cultures may better represent tumor biology and hence also be more suitable for cancer drug testing. However, stability of molecular and biological properties as well as reproducibility of drug response of these models over time remains an issue.

Methods: We performed longitudinal cell passaging, molecular profiling and drug response testing of 7 glioma spheroid models under standardized procedures. Next generation gene panel sequencing, 850K DNA methylome analysis and RNA sequencing were performed on early and late passages of each model and the respective primary tumor tissues in three models. Molecular profiles were compared to drug response data obtained for 231 clinically approved drugs.

Results: The three cell models for which corresponding primary tumor tissue was available retained the original tumor mutational profiles but showed in vitro culture-related differences at the epigenetic and transcriptional levels. The comparison of the early and late passage cultures revealed that these models remained molecularly stable over time and allowed for reproducible results in in vitro drug testing. Gene expression pathway analysis revealed possible mechanism linked to in vitro sensitivity or resistance to specific drugs, indicating the potential of gene expression-based prediction of therapy sensitivity.

Conclusion: Glioblastoma spheroid cultures remain molecularly and functionally stable over time and thus represent versatile glioma cell models for reproducible biomedical research in neurooncology. Gene expression profiles in these models may predict in vitro drug response.