Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma

Peter Sminia*, Helmut Acker, Hans Petter Eikesdal, Patricia Kaaijk, Per Øvind Enger, Ben Slotman, Rolf Bjerkvig

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)


Purpose: Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation. Materials and Methods: Tumour specimens of glioblastoma multiforme patients (n=16) were initiated as OMS. Following 20 Gy γ- irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by microelectrode pO2 measurements and pimonidazole immunostaining. Spheroids prepared from established human glioma cell lines were used as a reference. Results: Irradiation inhibited spheroid outgrowth by 12to 88 % relative to the non-irradiated controls. A large interpatient variation was noticed. Oxygen measurements revealed a gradual decrease in pO2 level from the periphery to the core of the spheroids, but the pO2 values remained within an oxygenated range. However, in the cell line spheroids an intermediate layer of hypoxia surrounding the central core was observed. Conclusion: Cell line spheroids with a hspoxic cell fraction and well-oxygenated OMS both show high resistance to irradiation, indicating that hypoxia may not be the biological factor determining the radioresistance of glioma spheroids in vitro.

Original languageEnglish
Pages (from-to)1461-1466
Number of pages6
JournalAnticancer Research
Issue number2 B
Publication statusPublished - Mar 2003
Externally publishedYes


  • Glioblastoma multiforme
  • Hypoxia
  • Irradiation
  • Organotypic multicellular spheroids


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