文章基本信息

标题：Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity
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作者：Yang Zhang ; Christelle Guillermier ; Thomas De Raedt 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：8
页码：1-30
DOI：10.1016/j.isci.2020.101355
语种：English
出版社：Elsevier
摘要：SummaryMalignant 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 as revealed by incorporation of glucose and glutamine tracers is thus a marker for tumor proliferation. Collectively, our data demonstrate that MIMS provides a powerful tool with which to dissect metabolic functions of individual cells within the native tumor environment.Graphical AbstractDisplay OmittedHighlights•A method to measure substrate utilization at single cancer cell resolution•Heterogeneity of glucose and glutamine utilization in murine tumors•Metabolic heterogeneity in proliferating and non-proliferating tumor cells•Metabolic heterogeneity correlates with proliferative growth and treatment resistanceBiological Sciences; Cancer Systems Biology