Biomedicine & Pharmacotherapy (Dec 2021)
Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
- A.C. Nickel,
- D. Picard,
- N. Qin,
- M. Wolter,
- K. Kaulich,
- M. Hewera,
- D. Pauck,
- V. Marquardt,
- G. Torga,
- S. Muhammad,
- W. Zhang,
- O. Schnell,
- H.-J. Steiger,
- D. Hänggi,
- E. Fritsche,
- N.-G. Her,
- D.-H. Nam,
- M.S. Carro,
- M. Remke,
- G. Reifenberger,
- U.D. Kahlert
Affiliations
- A.C. Nickel
- Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- D. Picard
- Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany
- N. Qin
- Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany
- M. Wolter
- Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- K. Kaulich
- Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- M. Hewera
- Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- D. Pauck
- Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- V. Marquardt
- Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- G. Torga
- Drug Development Unit, Sarah Cannon Research Institute, London, UK
- S. Muhammad
- Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- W. Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
- O. Schnell
- Department of Neurosurgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
- H.-J. Steiger
- Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- D. Hänggi
- Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany
- E. Fritsche
- Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
- N.-G. Her
- R&D Center, AIMEDBIO Inc., Seoul, South Korea
- D.-H. Nam
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, South Korea
- M.S. Carro
- Department of Neurosurgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
- M. Remke
- Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany
- G. Reifenberger
- Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany
- U.D. Kahlert
- Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Molecular and Experimental Surgery, Department of General, Visceral, Vascular, and Transplant Surgery, University Hospital Magdeburg, Magdeburg, Germany; Correspondence to: University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225 Dusseldorf, Germany.
- Journal volume & issue
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Vol. 144
p. 112278
Abstract
The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.
