Two distinct tumor phenotypes isolated from glioblastomas show different MRS characteristics

Frits Thorsen, Daniel Jirak, Jian Wang, Eva Sykova, Rolf Bjerkvig, Per Øyvind Enger, Albert van der Kogel, Milan Hajek*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

We have developed a human brain tumor model in immunodeficient rats that gradually changes its phenotype by serial passages in vivo, from a highly infiltrative, non-angiogenic one with numerous stem cell markers [low-generation (LG) tumor] to a more typical glioblastoma one with extensive angiogenesis and necrosis [high-generation (HG) tumor]. In this study we determined the metabolic properties of these two phenotypes, using 1H MRS. The LG tumors showed an intact blood-brain barrier and normal vascular morphology, as shown by MRI and Hoechst staining. In contrast, the HG tumors exhibited vascular leakage and necrosis. The animals with HG tumor had raised concentrations of choline and myo-inositol, and decreased concentrations of glutamate and N-acetylaspartate. In the LG tumor group, similar changes in metabolic concentrations were detected, although the alterations were more pronounced. The LG tumors also had higher concentrations of choline, taurine, and lactate. Subdividing the LG and HG tumors into large and small tumors revealed a significant increase in choline and decrease in glutamate as the LG tumors increased in size. Our results show that metabolic profiles produced by 1H MRS can be used to distinguish between two distinct glioblastoma phenotypes. More pronounced anaerobic metabolism was present in the LG stem-cell-like tumors, suggesting a more malignant phenotype.

Original languageEnglish
Pages (from-to)830-838
Number of pages9
JournalNMR in Biomedicine
Volume21
Issue number8
DOIs
Publication statusPublished - Oct 2008
Externally publishedYes

Keywords

  • Choline
  • Creatine
  • Glioblastoma
  • Glutamine
  • Lactate
  • Myo-inositol
  • N-acetylaspartate
  • Phosphocreatine
  • Proton MRS
  • Taurine
  • γ-aminobutyric acid

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