TY - JOUR
T1 - Different mechanisms underlie the metabolic response of GBM stem-like cells to ionizing radiation
T2 - Biological and MRS studies on effects of photons and carbon ions
AU - Palma, Alessandra
AU - Grande, Sveva
AU - Ricci-Vitiani, Lucia
AU - Luciani, Anna Maria
AU - Buccarelli, Mariachiara
AU - Biffoni, Mauro
AU - Dini, Valentina
AU - Cirrone, Giuseppe A.P.
AU - Ciocca, Mario
AU - Guidoni, Laura
AU - Pallini, Roberto
AU - Viti, Vincenza
AU - Rosi, Antonella
N1 - Funding Information:
Funding: This research was funded by National Institute of Nuclear Physics (INFN) in the framework of INFN Group V “RADIOSTEM” Experiment.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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 by1H 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.
AB - 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 by1H 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.
KW - Carbon ions
KW - Glioblastoma
KW - Metabolism
KW - MRS
KW - Photon beams
KW - Stem cells
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U2 - 10.3390/ijms21145167
DO - 10.3390/ijms21145167
M3 - Article
C2 - 32708312
AN - SCOPUS:85088236498
VL - 21
SP - 1
EP - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 14
M1 - 5167
ER -