Evidence for label-retaining tumour-initiating cells in human glioblastoma

Loic P. Deleyrolle, Angus Harding, Kathleen Cato, Florian A. Siebzehnrubl, Maryam Rahman, Hassan Azari, Sarah Olson, Brian Gabrielli, Geoffrey Osborne, Angelo Vescovi, Brent A. Reynolds

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1331-1343
Number of pages13
JournalBrain
Volume134
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • brain tumour
  • cancer stem cells
  • glioblastoma
  • label-retaining cells
  • tumour-initiating cells

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    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. (2011). Evidence for label-retaining tumour-initiating cells in human glioblastoma. Brain, 134(5), 1331-1343. https://doi.org/10.1093/brain/awr081