Different Mechanisms Underlie the Metabolic Response of GBM Stem-Like Cells to Ionizing Radiation: Biological and MRS Studies on Effects of Photons and Carbon Ions

Int J Mol Sci. 2020 Jul 21;21(14):5167. doi: 10.3390/ijms21145167.

Abstract

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with very poor prognosis, high recurrence rate, and failure of chemo-radiotherapy, mainly due to a small fraction of cells with stem-like properties (GSCs). To study the mechanisms of GSCs resistance to radiation, two GSC lines, named line #1 and line #83, with different metabolic patterns and clinical outcome, were irradiated with photon beams and carbon ions and assessed by 1H Magnetic Resonance Spectroscopy (MRS). Both irradiation modalities induced early cytotoxic effects in line #1 with small effects on cell cycle, whereas a proliferative G2/M cytostatic block was observed in line #83. MR spectroscopy signals from mobile lipids (ML) increased in spectra of line #1 after photon and C-ion irradiation with effects on lipid unsaturation level, whereas no effects were detected in line #83 spectra. Gamma-Aminobutyric Acid (GABA), glutamic acid (glu) and Phosphocreatine (pCr) signals showed a significant variation only for line #1 after carbon ion irradiation. Glucose (glc) level and lactate (Lac) extrusion behaved differently in the two lines. Our findings suggest that the differences in irradiation response of GSCs #1 and #83 lines are likely attributable to their different metabolic fingerprint rather than to the different radiation types.

Keywords: MRS; carbon ions; glioblastoma; metabolism; photon beams; stem cells.

MeSH terms

  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / radiotherapy
  • Cell Line, Tumor
  • G2 Phase Cell Cycle Checkpoints / radiation effects*
  • Glioblastoma / metabolism*
  • Glioblastoma / radiotherapy
  • Glucose / metabolism
  • Glutamic Acid / metabolism
  • Humans
  • Ions / metabolism
  • Lactic Acid / metabolism
  • Magnetic Resonance Spectroscopy*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / radiation effects
  • Phosphocreatine / metabolism
  • Photons / therapeutic use*
  • Radiation, Ionizing
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Ions
  • Phosphocreatine
  • Lactic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Glucose