title: Ultra-High Mass Resolution MALDI Imaging Mass Spectrometry of Proteins and Metabolites in a Mouse Model of Glioblastoma.
abstract: MALDI mass spectrometry imaging is able to simultaneously determine the spatial distribution of hundreds of molecules directly from tissue sections, without labeling and without prior knowledge. Ultra-high mass resolution measurements based on Fourier-transform mass spectrometry have been utilized to resolve isobaric lipids, metabolites and tryptic peptides. Here we demonstrate the potential of 15T MALDI-FTICR MSI for molecular pathology in a mouse model of high-grade glioma. The high mass accuracy and resolving power of high field FTICR MSI enabled tumor specific proteoforms, and tumor-specific proteins with overlapping and isobaric isotopic distributions to be clearly resolved. The protein ions detected by MALDI MSI were assigned to proteins identified by region-specific microproteomics (0.8 mm2regions isolated using laser capture microdissection) on the basis of exact mass and isotopic distribution. These label free quantitative experiments also confirmed the protein expression changes observed by MALDI MSI and revealed changes in key metabolic proteins, which were supported by in-situ metabolite MALDI MSI.
authors.affiliation: Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy.|Department of Chemistry and Industrial Chemistry - Università di Pisa - Via Giuseppe Moruzzi 13, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dilillo
authors.affiliation: Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ait-Belkacem
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Esteve
authors.affiliation: Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy.|NEST, Istituto Nanoscienze-National Research Council, 56127, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pellegrini
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Nicolardi
authors.affiliation: CNR Neuroscience Institute, Via Moruzzi 1, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Costa
authors.affiliation: CNR Neuroscience Institute, Via Moruzzi 1, 56124, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vannini
authors.affiliation: Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy.
authors.forename: E L de
authors.initials: EL
authors.lastname: Graaf
authors.affiliation: CNR Neuroscience Institute, Via Moruzzi 1, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Caleo
authors.affiliation: Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy. l.a.mcdonnell@outlook.com.|Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. l.a.mcdonnell@outlook.com.|Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. l.a.mcdonnell@outlook.com.
authors.forename: L A
authors.initials: LA
authors.lastname: McDonnell
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004734:Energy Metabolism; D005909:Glioblastoma / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D051379:Mice; D020543:Proteome; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome