Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice.

Détails

Ressource 1Télécharger: 40478_2021_Article_1232.pdf (4410.02 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_CB8B36AE633E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice.
Périodique
Acta neuropathologica communications
Auteur(s)
Cudalbu C., Bady P., Lai M., Xin L., Gusyatiner O., Hamou MF, Lepore M., Brouland JP, Daniel RT, Hottinger AF, Hegi ME
ISSN
2051-5960 (Electronic)
ISSN-L
2051-5960
Statut éditorial
Publié
Date de publication
04/08/2021
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
133
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes observed in patient derived orthotopic xenografts (PDOX) in the mouse and the corresponding patients' tumors. The evolution of metabolic changes, followed in vivo longitudinally by <sup>1</sup> H Magnetic Resonance Spectroscopy ( <sup>1</sup> H MRS) at ultra-high field, reflected growth and the invasive properties of the human glioblastoma transplanted into the brains of mice (PDOX). Comparison of MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel MRS analyses sampled across different areas of the patients' tumors. Pathway analyses of the transcriptome associated with the metabolite profiles of the PDOX, identified molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling. Specific analysis of expression signatures from the invaded mouse brain, revealed extent of invasion dependent induction of immune response, recapitulating respective signatures observed in glioblastoma. Integrating metabolic profiles and gene expression of highly invasive PDOX provided insights into progression and invasion associated mechanisms of extracellular matrix remodeling that is essential for cell-cell communication and regulation of cellular processes. Structural changes and biochemical properties of the extracellular matrix are of importance for the biological behavior of tumors and may be druggable. Ultra-high field MRS reveals to be suitable for in vivo monitoring of progression in the non-enhancing infiltration zone of glioblastoma.
Mots-clé
1H MRS at ultra-high fields (UHF), Glioblastoma, Invasion, Patient-derived orthotopic xenografts (PDOX), Transcriptome, Tumor host interaction, 1H MRS at ultra-high fields (UHF)
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/08/2021 14:36
Dernière modification de la notice
02/09/2021 6:40
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