biostudies-literatureZhang YNIDDK NIH HHSNCI NIH HHSNational Institutes of Health101355https://www.ebi.ac.uk/biostudies/studies/S-EPMC7390776biostudies-literatureUnknown23(8)Malignant tumors exhibit high degrees of genomic heterogeneity at the cellular level, leading to the view that subpopulations of tumor cells drive growth and treatment resistance. To examine the degree to which tumors also exhibit metabolic heterogeneity at the level of individual cells, we employed multi-isotope imaging mass spectrometry (MIMS) to quantify utilization of stable isotopes of glucose and glutamine along with a label for cell division. Mouse models of melanoma and malignant peripheral nerve sheath tumors (MPNSTs) exhibited striking heterogeneity of substrate utilization, evident in both proliferating and non-proliferating cells. We identified a correlation between metabolic heterogeneity, proliferation, and therapeutic resistance. Heterogeneity in metabolic substrate usage asiScienceImaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity.PMC7390776K08 DK105351DP2-CA216362DP2 CA216362Steinhauser MLDe Raedt TMaertens OMaas RLGoessling WZhang YGuillermier CLun MYimlamai DCox AGWhitney ACichowski KfalseImaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity.Malignant tumors exhibit high degrees of genomic heterogeneity at the cellular level, leading to the view that subpopulations of tumor cells drive growth and treatment resistance. To examine the degree to which tumors also exhibit metabolic heterogeneity at the level of individual cells, we employed multi-isotope imaging mass spectrometry (MIMS) to quantify utilization of stable isotopes of glucose and glutamine along with a label for cell division. Mouse models of melanoma and malignant peripheral nerve sheath tumors (MPNSTs) exhibited striking heterogeneity of substrate utilization, evident in both proliferating and non-proliferating cells. We identified a correlation between metabolic heterogeneity, proliferation, and therapeutic resistance. Heterogeneity in metabolic substrate usage as2020-01-01T00:00:00Z2020 Aug2025-04-26T21:23:50.248Z2025-04-06T16:47:55.743ZS-EPMC73907763271246610.1016/j.isci.2020.101355