Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity

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

doi:10.1016/j.isci.2020.101355

Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity

iScience. 2020 Aug 21;23(8):101355. doi: 10.1016/j.isci.2020.101355. Epub 2020 Jul 10.

Affiliations

¹ 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.
² Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Boston, MA, USA.
⁴ Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.
⁵ 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.
⁶ 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.

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.

Keywords: Biological Sciences; Cancer Systems Biology.

Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity

Authors

Affiliations

Abstract

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