The Glioblastoma Microenvironment: Morphology, Metabolism, and Molecular Signature of Glial Dynamics to Discover Metabolic Rewiring Sequence.
astrocytes
cross-talk
disease progression
glycolysis
high-grade glioma
hypoxia
metabolism
microglia
modules
oxidative phosphorylation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
24 Mar 2021
24 Mar 2021
Historique:
received:
22
02
2021
revised:
17
03
2021
accepted:
22
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
21
4
2021
Statut:
epublish
Résumé
Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment. This may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution, underlying the influence of the context and the timeline in anti-tumor therapeutic approaches. Besides the cancer metabolic strategies, here we review the modifications found in the GBM-associated glia, focusing on morphological, molecular, and metabolic features. We propose to analyze the GBM metabolic rewiring processes from a systems biology perspective. We aim at defining the crosstalk between GBM and the glial cells as modules. The complex networking may be expressed by metabolic modules corresponding to the GBM growth and spreading phases. Variation in the oxidative phosphorylation (OXPHOS) rate and regulation appears to be the most important part of the metabolic and functional heterogeneity, correlating with glycolysis and response to hypoxia. Integrated metabolic modules along with molecular and morphological features could allow the identification of key factors for controlling the GBM-stroma metabolism in multi-targeted, time-dependent therapies.
Identifiants
pubmed: 33804873
pii: ijms22073301
doi: 10.3390/ijms22073301
pmc: PMC8036663
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN2007
Organisme : Infrastructure for Systems Biology Europe-IT
ID : FOE 2019, 2020
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN2017-2017XJ38A4_003
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN2015-2015TM24JS_009
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