Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity.

Autor:	Zhang Y; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Guillermier C; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., De Raedt T; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Cox AG; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Maertens O; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Yimlamai D; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Boston, MA, USA., Lun M; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA., Whitney A; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA., Maas RL; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Goessling W; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Cichowski K; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Ludwig Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA., Steinhauser ML; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: msteinhauser@pitt.edu.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2020 Aug 21; Vol. 23 (8), pp. 101355. Date of Electronic Publication: 2020 Jul 10.
DOI:	10.1016/j.isci.2020.101355
Abstrakt:	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. Competing Interests: Declaration of Interests Competing interest reported C.G.: current employment (Zeiss); O.M.: current employment (Novartis); W.G.: consulting (Camp4); K.C.: consulting (Genentech); M.L.S.: consulting (Regeneron, Amgen). (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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