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 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 H-1 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 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 H-1 MRS can be used to distinguish between two distinct glioblastoma phenotypes. More pronounced anaerobic metabolism was present ill the LG stem-cell-like tumors, suggesting a more malignant phenotype.