resumo
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.
palavras-chave
MAGNETIC-RESONANCE-SPECTROSCOPY; DUCTAL ADENOCARCINOMA; BIOMARKER; DISCOVERY; DISEASE; INHIBITION; CHOLINE; CELLS; NMR
categoria
Biochemistry & Molecular Biology
autores
Carneiro, TJ; Pinto, J; Serrao, EM; Barros, AS; Brindle, KM; Gil, AM
nossos autores
Ana Maria Pissarra Coelho Gil
Professor Associado com Agregação
António de Sousa Barros
Bolseiro de pós-Doutoramento
Joana Isabel Monteiro Pinto
Bolseiro de pós-Doutoramento
Tatiana João Ribeiro Gonçalves Carneiro
Estudante de doutoramentoProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC). AG also acknowledges the Portuguese National NMR Network (RNRMN), partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020; POCI and PORL and FCT through PIDDAC), and FCT grant SFRH/BSAB/113663/2015 (AMG). JP and AB are grateful to CICECO-Aveiro Institute of Materials for postdoc grants. Work in KB's laboratory is funded by grants from Cancer Research UK (C197/A29580, C197/A17242).