Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity

Autor: Yang Zhang, Christelle Guillermier, Thomas De Raedt, Andrew G. Cox, Ophelia Maertens, Dean Yimlamai, Mingyue Lun, Adam Whitney, Richard L. Maas, Wolfram Goessling, Karen Cichowski, Matthew L. Steinhauser
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: iScience, Vol 23, Iss 8, Pp 101355- (2020)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2020.101355
Popis: Summary: 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.
Databáze: Directory of Open Access Journals