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    Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity

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    Author
    Zhang, Y; Guillermier, C; De Raedt, T; Cox, AG; Maertens, O; Yimlamai, D; Lun, M; Whitney, A; Maas, RL; Goessling, W; ...
    Date
    2020-08-21
    Source Title
    iScience
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Cox, Andrew
    Affiliation
    Biochemistry and Molecular Biology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Zhang, Y., Guillermier, C., De Raedt, T., Cox, A. G., Maertens, O., Yimlamai, D., Lun, M., Whitney, A., Maas, R. L., Goessling, W., Cichowski, K. & Steinhauser, M. L. (2020). Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity. ISCIENCE, 23 (8), https://doi.org/10.1016/j.isci.2020.101355.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/251514
    DOI
    10.1016/j.isci.2020.101355
    Abstract
    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 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.

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