Author(s): Martins, Filipa ; van der Kellen, David ; Gonçalves, Luís G. ; Serpa, Jacinta
Date: 2023
Persistent ID: http://hdl.handle.net/10362/159539
Origin: Repositório Institucional da UNL
Subject(s): cancer metabolism; gene expression profiles; glioblastoma; metabolic remodeling; metabolomics; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology(all); SDG 3 - Good Health and Well-being
Funding Information: The institutions are funded by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), to MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020), and the Associated Laboratory LS4FUTURE (LA/P/0087/2020). Filipa Martins was funded by an FCT individual Ph.D. fellowship (2020.04780.BD). Luis G. Gonçalves was financed by a FCT contract according to DL57/2016, (SFRH/BPD/111100/2015). This work benefited from access to CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016. Publisher Copyright: © 2023 by the authors.
Glioblastoma (GBM) is the most lethal central nervous system (CNS) tumor, mainly due to its high heterogeneity, invasiveness, and proliferation rate. These tumors remain a therapeutic challenge, and there are still some gaps in the GBM biology literature. Despite the significant amount of knowledge produced by research on cancer metabolism, its implementation in cancer treatment has been limited. In this study, we explored transcriptomics data from the TCGA database to provide new insights for future definition of metabolism-related patterns useful for clinical applications. Moreover, we investigated the impact of key metabolites (glucose, lactate, glutamine, and glutamate) in the gene expression and metabolic profile of two GBM cell lines, U251 and U-87MG, together with the impact of these organic compounds on malignancy cell features. GBM cell lines were able to adapt to the exposure to each tested organic compound. Both cell lines fulfilled glycolysis in the presence of glucose and were able to produce and consume lactate. Glutamine dependency was also highlighted, and glutamine and glutamate availability favored biosynthesis observed by the increase in the expression of genes involved in fatty acid (FA) synthesis. These findings are relevant and point out metabolic pathways to be targeted in GBM and also reinforce that patients’ metabolic profiling can be useful in terms of personalized medicine.
