Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolism
Anastasia Tsyben, Andreas Dannhorn, Grégory Hamm, Matthaios Pitoulias, Dominique‐Laurent Couturier, Ashley Sawle, Mayen Briggs, Alan J. Wright, Cara Brodie, Lee Mendil, Jodi L. Miller, Eleanor C Williams, Lovisa Franzén, Grand De Jong, Tannia Gracia, Fani Memi, Omer Ali Bayraktar, R. Adapa, Jyotsna U. Rao, Ariadna González-Fernández, Josephine Bunch, Zoltán Takáts, Simon T. Barry, Richard J. A. Goodwin, Richard Mair, Kevin M. Brindle
Abstract
Abstract Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities 1–3 . 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- 13 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.