National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy.
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
Biomolecules. 2022 Jul 28;12(8):1051. doi: 10.3390/biom12081051.
Glioblastoma is the most common and lethal primary malignant brain tumor in adults. Glioblastoma stem cells (GSCs) promote and are responsible for glioblastoma intratumoral heterogeneity and therapy resistance, due to their two main features: self-renewal and differentiation. Lipids have important biological and physiological functions that are critical for understanding the regulation and control of stem cell fate; lipid metabolism and related unsaturation levels play a possible role as the target of therapeutics to overcome glioblastoma radioresistance. This paper aimed at an in-depth analysis of 13 GSC mesenchymal (MES) lines, two subclones, and a stabilized glioblastoma line (T98G) by magnetic resonance spectroscopy (MRS). Particularly, 2D MRS was used to investigate lipid unsaturation behavior during growth in culture and after treatment with etomoxir and photon beams. MES lines, although belonging to the same genetic and metabolic cluster, showed metabolic heterogeneity when observed by MRS, focusing on lipid signals. Nonetheless, the observed unsaturation level stability for two representative lines after stressful treatments suggests unusual robustness of the unsaturation levels for each line, as a peculiar and intrinsic characteristic of GSCs.
胶质母细胞瘤是成年人中最常见和最致命的原发性恶性脑肿瘤。胶质母细胞瘤干细胞(GSCs)由于其两个主要特征:自我更新和分化,促进并负责胶质母细胞瘤肿瘤内异质性和治疗耐药性。脂质具有重要的生物学和生理学功能,对于理解干细胞命运的调节和控制至关重要;脂质代谢和相关不饱和水平可能作为克服胶质母细胞瘤放射抗性的治疗靶点。本文旨在通过磁共振波谱(MRS)对 13 个 GSC 间质(MES)系、两个亚克隆和一个稳定的胶质母细胞瘤系(T98G)进行深入分析。特别是,2D-MRS 用于研究在培养过程中生长和用 etomoxir 和光子束处理后的脂质不饱和行为。MES 系虽然属于同一遗传和代谢群,但通过 MRS 观察到代谢异质性,重点是脂质信号。尽管在应激处理后两个有代表性的系观察到不饱和水平的稳定性,但这表明每个系的不饱和水平具有异常的稳健性,这是 GSCs 的一个特殊和内在特征。