Glioblastoma Stem-Like Cells (GSCs) with Mesenchymal Signature: Lipid Profiles of Mobile Lipids Obtained with MRS before and after Radio/Chemical Treatments

Abstract

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.

Prognostic Value of Choline and Other Metabolites Measured Using 1H-Magnetic Resonance Spectroscopy in Gliomas: A Meta-Analysis and Systemic Review

“…Grande et al applied MRS in glioblastoma stem-like cells and detected multiple metabolites in vitro, indicating an important role of mitochondrial fatty oxidation in energy supplements in glioblastoma stem-like cells [30]. They also discovered specific metabolic signatures of glioblastoma stem-like cells after stressful treatments via MRS detection [31]. All the studies suggest more advanced utilization of MRS in metabolic investigations and clinical practice, and further investigations could be conducted.…”

Using the metabolite alterations monitoring the AEG-1 expression level and cell biological behaviour of U251 cell in vitro

“…1 H MRS provides irreplaceable information for the diagnosis and therapeutic monitoring of tumors, particularly gliomas [21][22][23]. Studies have shown that the metabolite ratio has a specific value in differentiating treatment-related changes (radiation necrosis and tumor pseudoprogression) from tumor recurrence in gliomas [24][25][26]. Total choline (tCho) is considered a biomarker reflecting the state of cell membrane turnover and has been widely used to identify tumor areas with excessive cell proliferation and for the therapeutic monitoring of gliomas [27,28].…”

“…Few studies have investigated the relationship between metabolite alterations and oncogenic expression [31]. In in vitro MRS research, the scientific detection of metabolites could be analyzed by combining certain gene expression and cell biological behaviors [23,25], which could provide excellent feedback on cellular states in tumor progression. These in vitro research achievements may be transformed into in Vivo MRS studies to sufficiently comprehend new clinical MRS discoveries [32].…”