Evidence for label-retaining tumour-initiating cells in human glioblastoma
Open accessAbstract
Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.
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Glioblastoma tumors contain a diverse mixture of growing, senescent, quiescent, and dying cells.
“GBM tumors are known to harbor an exceptionally diverse admixture of growing, senescent, quiescent, and dying cells16, 17.”
From Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate (2016) · cites this paper as [17]
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- Authors
- Deleyrolle, L. P., Harding, A., Cato, K., Siebzehnrubl, F. A., Rahman, M., Azari, H., Olson, S., Gabrielli, B., Osborne, G., Vescovi, A., & Reynolds, B. A.
- Affiliations
- The University of Queensland (AU)
- University of Florida (US)
- Shiraz University of Medical Sciences (IR)
- University of Milano-Bicocca (IT)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04-22
- Volume
- 134
- Issue
- 5
- Pages
- 1331-1343
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3097894
- OpenAlex
- W1984483719
- Cited by
- 182
- References
- 60
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 12 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 15 · 2017: 11 · 2016: 18 · 2015: 17 · 2014: 11 · 2013: 14 · 2012: 13
- FWCI
- 6.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Cancer Institute (R21CA141020)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- glioblastoma, cancer stem cells, label-retaining cells, tumor heterogeneity, brain tumors, cell proliferation, therapeutic target
- MeSH terms
- Animals, Astrocytes, Brain Neoplasms, Cell Cycle, Cell Differentiation, Cells, Cultured, Female, Flow Cytometry, Fluoresceins, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Intermediate Filament Proteins, Neoplasm Transplantation, Nerve Tissue Proteins, Nuclear Proteins, Succinimides, Antigens, CD, Mice, SCID, Cell Cycle Proteins, O Antigens, Mice, Neural Stem Cells, Minichromosome Maintenance Complex Component 2, Nestin
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