Phenotypic and functional characterization of Glioblastoma cancer stem cells identified through 5-aminolevulinic acid-assisted surgery [corrected]

J Neurooncol. 2014 Feb;116(3):505-13. doi: 10.1007/s11060-013-1348-3. Epub 2014 Jan 9.


5-aminolevulinic acid (5-ALA) introduction in the surgical management of Glioblastoma (GBM) enables the intra-operatively identification of cancer cells in the mass by means of fluorescence. Here, we analyzed the phenotype of GBM cells isolated from distinct tumour areas determined by 5-ALA (tumour core, 5-ALA intense and vague layers) and the potency of 5-ALA labelling in identifying GBM cells and cancer stem cells (CSCs) in the mass. 5-ALA identified distinct layers in the mass, with less differentiated cells residing in the core of the tumour. 5-ALA was able to stain up to 68.5% of CD133(+) cells in the 5-ALA intense layer and, although 5-ALA(+) cells retrieved from different tumour areas contained a similar proportion of CD133(+) cells (range 27.5-35.6%), those from the vague layer displayed the lowest ability to self-renew. In conclusion, our data demonstrate that a substantial amount of GBM cells and CSCs in the mass are able to avoid 5-ALA labelling and support the presence of heterogenic CSC populations in the GBM mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Aminolevulinic Acid* / metabolism
  • Antigens, CD / metabolism
  • Biopsy
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / surgery
  • Flow Cytometry
  • Glioblastoma / pathology*
  • Glioblastoma / surgery
  • Glycoproteins / metabolism
  • Humans
  • Ki-67 Antigen / metabolism
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Nerve Tissue Proteins / metabolism
  • Peptides / metabolism
  • Photosensitizing Agents* / metabolism


  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • Ki-67 Antigen
  • Nerve Tissue Proteins
  • PROM1 protein, human
  • Peptides
  • Photosensitizing Agents
  • Aminolevulinic Acid