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

International Journal of Molecular Sciences

Mario Ciocca¹  Laura Guidoni²  Vincenza Viti³  Lucia Ricci-Vitiani⁴  Mariachiara Buccarelli⁴  Mauro Biffoni⁴  Roberto Pallini⁵  Alessandra Palma⁵  Antonella Rosi⁵  Sveva Grande⁵  Anna Maria Luciani⁵  Valentina Dini⁵  Giuseppe A.P. Cirrone⁶ 

[1] ;Centro Nazionale di Adroterapia Oncologica (CNAO) - National Center for Oncological Hadrontherapy, 27100 Pavia, Italy;Department of Neuroscience, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy;National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy;National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 95123 Catania, Italy;

关键词: glioblastoma;    stem cells;    metabolism;    MRS;    photon beams;    carbon ions;   

DOI  :  10.3390/ijms21145167

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown