Glioma Stem Cell Lines Expanded in Adherent Culture Have Tumor-Specific Phenotypes and Are Suitable for Chemical and Genetic Screens
Open accessAbstract
Human brain tumors appear to have a hierarchical cellular organization suggestive of a stem cell foundation. In vitro expansion of the putative cancer stem cells as stable cell lines would provide a powerful model system to study their biology. Here, we demonstrate routine and efficient derivation of adherent cell lines from malignant glioma that display stem cell properties and initiate high-grade gliomas following xenotransplantation. Significantly, glioma neural stem (GNS) cell lines from different tumors exhibit divergent gene expression signatures and differentiation behavior that correlate with specific neural progenitor subtypes. The diversity of gliomas may, therefore, reflect distinct cancer stem cell phenotypes. The purity and stability of adherent GNS cell lines offer significant advantages compared to "sphere" cultures, enabling refined studies of cancer stem cell behavior. A proof-of-principle live cell imaging-based chemical screen (450 FDA-approved drugs) identifies both differential sensitivities of GNS cells and a common susceptibility to perturbation of serotonin signaling.
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Only cells maintained in serum-free media retain their original tumour-specific phenotype.
“Only cells maintained in serum-free media retain their original tumour-specific phenotype64.”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [64]
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- Authors
- Pollard, S. M., Yoshikawa, K., Clarke, I. D., Danovi, D., Stricker, S., Russell, R., Bayani, J., Head, R., Lee, M., Bernstein, M., Squire, J. A., Smith, A., & Dirks, P.
- Affiliations
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Toronto (CA)
- University Health Network (CA)
- Western General Hospital (GB)
- Queen's University (CA)
- Corresponding author
- Pollard, Steven M.
- Dirks, Peter
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 4
- Issue
- 6
- Pages
- 568-580
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2081758137
- Cited by
- 1,025
- References
- 48
- Citations by year
- 2026: 23 · 2025: 34 · 2024: 41 · 2023: 56 · 2022: 60 · 2021: 82 · 2020: 66 · 2019: 59 · 2018: 69 · 2017: 74 · 2016: 68 · 2015: 66 · 2014: 62 · 2013: 66 · 2012: 69
- FWCI
- 32.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1543 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Genome Canada
- Ontario Genomics
- Ontario Genomics Institute
- Stem Cell Network
- Cancer Research UK
- University of Toronto
- Hospital for Sick Children
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Christ's College, University of Cambridge
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- glioma, cancer stem cells, adherent culture, neural stem cells, tumor heterogeneity, xenotransplantation, gene expression signatures, chemical screen, drug sensitivity, serotonin signaling, high-grade glioma
- MeSH terms
- Animals, Cell Adhesion, Drug Screening Assays, Antitumor, Glioma, Humans, Serotonin, Transplantation, Heterologous, Neoplastic Stem Cells, Mice, SCID, Gene Expression Profiling, Cell Line, Tumor, Culture Techniques, Mice
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