Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model
Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompan...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.937865/full |
| _version_ | 1817998527350964224 |
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| author | Tatiana J. Carneiro Joana Pinto Eva M. Serrao Eva M. Serrao António S. Barros Kevin M. Brindle Kevin M. Brindle Ana M. Gil |
| author_facet | Tatiana J. Carneiro Joana Pinto Eva M. Serrao Eva M. Serrao António S. Barros Kevin M. Brindle Kevin M. Brindle Ana M. Gil |
| author_sort | Tatiana J. Carneiro |
| collection | DOAJ |
| description | Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompanying PCa progression. Using multivariate analysis a 10-metabolite metabolic signature specific to Pt tissue was found to distinguish the benign condition from both normal tissue and precancerous tissue (low grade pancreatic intraepithelial neoplasia, PanIN, lesions). The mice pancreata showed significant changes in the progression from normal tissue, through low-grade and high-grade PanIN lesions to pancreatic ductal adenocarcinoma (PDA). These included increased lactate production, amino acid changes consistent with enhanced anaplerosis, decreased concentrations of intermediates in membrane biosynthesis (phosphocholine and phosphoethanolamine) and decreased glycosylated uridine phosphates, reflecting activation of the hexosamine biosynthesis pathway and protein glycosylation. |
| first_indexed | 2024-04-14T02:54:26Z |
| format | Article |
| id | doaj.art-399346a3c6134faaadb8d2f0b107f229 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-14T02:54:26Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-399346a3c6134faaadb8d2f0b107f2292022-12-22T02:16:10ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-08-01910.3389/fmolb.2022.937865937865Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse modelTatiana J. Carneiro0Joana Pinto1Eva M. Serrao2Eva M. Serrao3António S. Barros4Kevin M. Brindle5Kevin M. Brindle6Ana M. Gil7CICECO - Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Aveiro, PortugalCICECO - Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Aveiro, PortugalCancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United KingdomDepartment of Biochemistry, University of Cambridge, Cambridge, United KingdomCICECO - Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Aveiro, PortugalCancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United KingdomDepartment of Biochemistry, University of Cambridge, Cambridge, United KingdomCICECO - Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Aveiro, PortugalUntargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompanying PCa progression. Using multivariate analysis a 10-metabolite metabolic signature specific to Pt tissue was found to distinguish the benign condition from both normal tissue and precancerous tissue (low grade pancreatic intraepithelial neoplasia, PanIN, lesions). The mice pancreata showed significant changes in the progression from normal tissue, through low-grade and high-grade PanIN lesions to pancreatic ductal adenocarcinoma (PDA). These included increased lactate production, amino acid changes consistent with enhanced anaplerosis, decreased concentrations of intermediates in membrane biosynthesis (phosphocholine and phosphoethanolamine) and decreased glycosylated uridine phosphates, reflecting activation of the hexosamine biosynthesis pathway and protein glycosylation.https://www.frontiersin.org/articles/10.3389/fmolb.2022.937865/fullpancreatitispancreatic cancerPanINpancreatic ductal adenocarcinomaKRASmetabolomics |
| spellingShingle | Tatiana J. Carneiro Joana Pinto Eva M. Serrao Eva M. Serrao António S. Barros Kevin M. Brindle Kevin M. Brindle Ana M. Gil Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model Frontiers in Molecular Biosciences pancreatitis pancreatic cancer PanIN pancreatic ductal adenocarcinoma KRAS metabolomics |
| title | Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model |
| title_full | Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model |
| title_fullStr | Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model |
| title_full_unstemmed | Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model |
| title_short | Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model |
| title_sort | metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant kras mouse model |
| topic | pancreatitis pancreatic cancer PanIN pancreatic ductal adenocarcinoma KRAS metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.937865/full |
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