Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolismUniv Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
AstraZeneca, Cambridge Biomed Campus, Cambridge, England; Univ Cambridge, Cambridge Stem Cell Inst, Cambridge, England.
Wellcome Genome Campus, Wellcome Sanger Inst, Cambridge, England.
Wellcome Genome Campus, Wellcome Sanger Inst, Cambridge, England.
Wellcome Genome Campus, Wellcome Sanger Inst, Cambridge, England.
Wellcome Genome Campus, Wellcome Sanger Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
Natl Phys Lab, Teddington, England.
Natl Phys Lab, Teddington, England; Imperial Coll, Dept Metab Digest & Reprod, London, England.
Imperial Coll, Dept Metab Digest & Reprod, London, England.
AstraZeneca, Cambridge Biomed Campus, Cambridge, England.
AstraZeneca, Integrated BioAnal Clin Pharmacol & Safety Sci R&D, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England; Cambridge Biomed Campus, Dept Clin Neurosci, Cambridge, England.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England; Univ Cambridge, Dept Biochem, Cambridge, England.
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2025 (English)In: Nature Metabolism, E-ISSN 2522-5812, Vol. 7, no 5Article in journal (Refereed) Published
Abstract [en]
Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities1, 2-3. Here we identified three metabolic subtypes: glycolytic, oxidative and a mix of glycolytic and oxidative, using mass spectrometry imaging of rapidly excised tumour sections from two patients with GB who were infused with [U-13C]glucose and from spatial transcriptomic analysis of contiguous sections. The phenotypes are not correlated with microenvironmental features, including proliferation rate, immune cell infiltration and vascularization, are retained when patient-derived cells are grown in vitro or as orthotopically implanted xenografts and are robust to changes in oxygen concentration, demonstrating their cell-intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes is large enough to be detected using clinically applicable metabolic imaging techniques. A limitation of the study is that it is based on only two patient tumours, albeit on multiple sections, and therefore represents a proof-of-concept study.
Place, publisher, year, edition, pages
Springer Nature , 2025. Vol. 7, no 5
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:kth:diva-365951DOI: 10.1038/s42255-025-01293-yISI: 001490583900001PubMedID: 40389678Scopus ID: 2-s2.0-105005945919OAI: oai:DiVA.org:kth-365951DiVA, id: diva2:1981073
Note
QC 20250703
2025-07-032025-07-032025-07-03Bibliographically approved