Antitumor compound testing in glioblastoma organotypic brain cultures

J Biomol Screen. 2011 Sep;16(8):805-17. doi: 10.1177/1087057111414895. Epub 2011 Aug 1.


Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor. Identification of new therapeutic regimens is urgently needed. A major challenge remains the development of a relevant in vitro model system with the necessary capacity and flexibility to profile compounds. The authors have developed and characterized a 3D culture system of brain cells (brain Hi-Spot) where GBM-derived cells can be incorporated (GBM/brain Hi-Spot). Immuno-fluorescence and electrophysiological recordings demonstrate that brain Hi-Spots recapitulate many features of brain tissue. Within this tissue, GBM-derived cell growth is monitored using a fluorescence assay. GBM-derived cells growing in Hi-Spots form tumor nodules that display properties of GBM such as 5-Ala positive staining, an acidic environment, and tumor-surrounding astrocyte activation. Temozolomide inhibits GBM growth in brain Hi-Spots, but it is not effective in 2D cultures. Other chemotherapeutics that have proven to be inefficient in GBM treatment display low activity against GBM-derived cells growing in brain Hi-Spots in comparison to their activity against GBM 2D cultures. These findings suggest that GBM/brain Hi-Spots represent a simple system to culture cells derived from brain tumors in an orthotopic environment in vitro and that the system is reliable to test GBM targeting compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / analysis
  • Animals
  • Antineoplastic Agents / pharmacology
  • Astrocytes / cytology
  • Brain / drug effects*
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Culture Techniques*
  • Cell Proliferation
  • Diffusion Chambers, Culture
  • Drug Screening Assays, Antitumor*
  • Electrophysiology
  • Fluorescent Antibody Technique
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Histocytochemistry
  • Rats
  • Rats, Wistar
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Aminolevulinic Acid