Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolism
Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities<sup>1-3</sup>. 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-<sup>13</sup>C]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.
Authors
- Omer Ali Bayraktar (ORCID: https://orcid.org/0000-0001-6055-277X)
- Josephine Bunch (ORCID: https://orcid.org/0000-0002-4257-1296)
- Kevin Michael Brindle (ORCID: https://orcid.org/0000-0003-3883-6287)
- Fani Memi (ORCID: https://orcid.org/0000-0002-3685-1988)
- Richard J. A. Goodwin (ORCID: https://orcid.org/0000-0001-5699-8488)
- Ariadna González-Fernández (ORCID: https://orcid.org/0009-0003-3225-4718)
- Anastasia Tsyben (ORCID: https://orcid.org/0009-0001-7864-9526)
- Grégory Hamm (ORCID: https://orcid.org/0000-0002-0769-9411)
- Eleanor C Williams (ORCID: https://orcid.org/0000-0002-8023-9550)
- Alan J. Wright (ORCID: https://orcid.org/0000-0002-4577-5681)
- Simon T. Barry (ORCID: https://orcid.org/0000-0002-8511-0588)
- Zoltán Takáts (ORCID: https://orcid.org/0000-0002-0795-3467)
- Tannia Gracia
- Mayen Briggs
- Ashley Sawle (ORCID: https://orcid.org/0000-0002-2985-5059)
- Jyotsna U. Rao
- Matthaios Pitoulias (ORCID: https://orcid.org/0000-0002-9814-0604)
- Lovisa Franzén (ORCID: https://orcid.org/0000-0003-3755-718X)
- Andreas Dannhorn (ORCID: https://orcid.org/0000-0002-1087-4057)
- Lee Mendil (ORCID: https://orcid.org/0000-0003-4110-8061)
- Jodi L. Miller (ORCID: https://orcid.org/0000-0001-6870-204X)
- Dominique‐Laurent Couturier (ORCID: https://orcid.org/0000-0001-5774-5036)
- Richard James Mair (ORCID: https://orcid.org/0000-0001-8235-5689)
- Cara Brodie (ORCID: https://orcid.org/0009-0004-7146-8855)
- R. Adapa (ORCID: https://orcid.org/0000-0002-9845-8532)
- G. de Jong
Institutions
- AstraZeneca (United Kingdom) (GB)
- National Physical Laboratory (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Science for Life Laboratory (SE)
- Cancer Research UK (GB)
- Wellcome Sanger Institute (GB)
- Cancer Research UK Cambridge Center (GB)
- AstraZeneca (Finland) (FI)
- Cambridge Research Biochemicals (United Kingdom) (GB)
- AstraZeneca (Spain) (ES)
- Imperial College London (GB)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2025-05-19
- DOI
- https://doi.org/10.1038/s42255-025-01293-y
- Citations
- 9
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 14.63
Funders
- Cancer Research UK