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

• Published in: International journal of molecular sciences Vol. 21; no. 14; p. 5167
• Main Authors: Palma, Alessandra, Grande, Sveva, Ricci-Vitiani, Lucia, Luciani, Anna Maria, Buccarelli, Mariachiara, Biffoni, Mauro, Dini, Valentina, Cirrone, Giuseppe A P, Ciocca, Mario, Guidoni, Laura, Pallini, Roberto, Viti, Vincenza, Rosi, Antonella
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.07.2020; MDPI
• Subjects: Apoptosis; Biomarkers; Brain cancer; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Brain tumors; Carbon; carbon ions; Cell cycle; Cell growth; Cell Line, Tumor; Charged particles; Cytotoxicity; Extrusion; G2 Phase Cell Cycle Checkpoints - radiation effects; gamma-Aminobutyric Acid - metabolism; Gene expression; Genotype & phenotype; Glioblastoma; Glioblastoma - metabolism; Glioblastoma - radiotherapy; Glucose - metabolism; Glutamic acid; Glutamic Acid - metabolism; Humans; Hypotheses; Ion beams; Ion irradiation; Ionizing radiation; Ions - metabolism; Lactic acid; Lactic Acid - metabolism; Line spectra; Lipids; Magnetic Resonance Spectroscopy; Medical prognosis; Metabolic response; Metabolism; Metabolites; MRS; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - radiation effects; Patients; Phosphocreatine; Phosphocreatine - metabolism; Photon beams; Photons; Photons - therapeutic use; Principal components analysis; Radiation therapy; Radiation tolerance; Radiation, Ionizing; stem cells; Tumors; γ-Aminobutyric acid; Italy; carbon ions; stem cells; metabolism; photon beams; glioblastoma; MRS
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21145167

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 H 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.