In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues.

Autor:	Young LEA; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA.; Markey Cancer Center, University of Kentucky, Lexington, KY, USA., Conroy LR; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA., Clarke HA; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA., Hawkinson TR; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA., Bolton KE; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA., Sanders WC; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA., Chang JE; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA., Webb MB; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA., Alilain WJ; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA.; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA., Vander Kooi CW; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA.; Markey Cancer Center, University of Kentucky, Lexington, KY, USA., Drake RR; Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA., Andres DA; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA., Badgett TC; Pediatric Hematology-Oncology, College of Medicine, University of Kentucky, Lexington, KY, USA., Wagner LM; Pediatric Hematology-Oncology, Duke University, Durham, NC, USA., Allison DB; Department of Pathology and Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA., Sun RC; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA.; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA.; Department of Biochemistry & Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.; Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA., Gentry MS; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA.; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.; Department of Biochemistry & Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.; Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA.
Jazyk:	angličtina
Zdroj:	EMBO molecular medicine [EMBO Mol Med] 2022 Nov 08; Vol. 14 (11), pp. e16029. Date of Electronic Publication: 2022 Sep 05.
DOI:	10.15252/emmm.202216029
Abstrakt:	Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma. (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze:	MEDLINE
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