Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model

Abstract

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.

Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma

“…The technique presents the unique advantage of probing real-time metabolic fluxes in vivo and therefore does not require excising the tumor sample. In particular, HP 13 C-MRS can image the real-time conversion of HP-[1-13 C]pyruvate to [1- 13 C]lactate, catalyzed by LDH, and is a promising preclinical and clinical imaging biomarker of aggressiveness and early treatment response [159][160][161]. The technique measures the 13 C-lactate-to- 13 C-pyruvate ratio, reflecting the activity of LDH.…”