Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts

Version 1 : Received: 19 January 2022 / Approved: 20 January 2022 / Online: 20 January 2022 (19:42:29 CET)

A peer-reviewed article of this Preprint also exists.

Miyazaki, Y.; Mori, N.; Akagi, Y.; Oda, T.; Kida, Y.S. Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts. Cancers 2022, 14, 1375. Miyazaki, Y.; Mori, N.; Akagi, Y.; Oda, T.; Kida, Y.S. Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts. Cancers 2022, 14, 1375.

Journal reference: Cancers 2022, 14, 1375
DOI: 10.3390/cancers14061375

Abstract

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment perform glycolysis to produce energy, i.e., ATP. Since the origin of CAFs is unidentified, it is not determined whether the intracellular metabolism transitions from oxidative phosphorylation (OXPHOS) to glycolysis when normal tissue fibroblasts differentiate into CAFs. In this study, we established an experimental system and induced the in vitro differentiation of mesenchymal stem cells (MSCs) to CAFs. Additionally, we performed metabolomic and RNA-sequencing analyses before and after differentiation to investigate changes in the intracellular metabolism. Consequently, we discovered that OXPHOS, which was the primary intracellular metabolism in MSCs, was reprogrammed to glycolysis. In addition, we identified CAF-specific metabolites that were expressed during this reprogramming and determined their presence in the pancreatic tumor tissues of mouse models. Thus, we conclude that normal tissue fibroblasts that differentiate into CAFs undergo a metabolic reprogramming from OXPHOS to glycolysis. Moreover, we identified the CAF-specific metabolites expressed during metabolic reprogramming as potential future biomarkers for pancreatic cancer.

Keywords

cancer-associated fibroblasts; tumor microenvironment; pancreatic cancer; intracellular metabolism; glycolysis; oxidative phosphorylation; cell differentiation

Subject

BIOLOGY, Physiology

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