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Sci Rep. 2017 Apr 4;7(1):603. doi: 10.1038/s41598-017-00703-w.

Ultra-High Mass Resolution MALDI Imaging Mass Spectrometry of Proteins and Metabolites in a Mouse Model of Glioblastoma.

Author information

1
Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy.
2
Department of Chemistry and Industrial Chemistry - Università di Pisa - Via Giuseppe Moruzzi 13, 56124, Pisa, Italy.
3
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
4
NEST, Istituto Nanoscienze-National Research Council, 56127, Pisa, Italy.
5
CNR Neuroscience Institute, Via Moruzzi 1, 56124, Pisa, Italy.
6
Fondazione Pisana per la Scienza ONLUS - Via Panfilo Castaldi 2, 56121, Pisa, Italy. l.a.mcdonnell@outlook.com.
7
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. l.a.mcdonnell@outlook.com.
8
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. l.a.mcdonnell@outlook.com.

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 mm2 regions 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.

PMID:
28377615
PMCID:
PMC5429601
DOI:
10.1038/s41598-017-00703-w
[Indexed for MEDLINE]
Free PMC Article

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