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

Brain. 2011 May;134(Pt 5):1331-43. doi: 10.1093/brain/awr081. Epub 2011 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Fluoresceins / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Mice, SCID
  • Minichromosome Maintenance Complex Component 2
  • Neoplasm Transplantation / pathology
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Nuclear Proteins / metabolism
  • O Antigens / metabolism
  • Succinimides / metabolism


  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Antigens, CD
  • Cell Cycle Proteins
  • Fluoresceins
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Nuclear Proteins
  • O Antigens
  • Succinimides
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2