Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts
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...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/6/1375 |
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| author | Yoshihiro Miyazaki Nobuhito Mori Yuka Akagi Tatsuya Oda Yasuyuki S. Kida |
| author_facet | Yoshihiro Miyazaki Nobuhito Mori Yuka Akagi Tatsuya Oda Yasuyuki S. Kida |
| author_sort | Yoshihiro Miyazaki |
| collection | DOAJ |
| description | 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. Furthermore, we analyzed the metabolites in pancreatic tumor tissues in a mice model. The metabolites extracted as candidates in the in vitro experiments were also detected in the in vivo experiments. 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. |
| first_indexed | 2024-03-09T20:03:03Z |
| format | Article |
| id | doaj.art-93dba101d8124dab8462f93a85109827 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:03:03Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-93dba101d8124dab8462f93a851098272023-11-24T00:40:02ZengMDPI AGCancers2072-66942022-03-01146137510.3390/cancers14061375Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated FibroblastsYoshihiro Miyazaki0Nobuhito Mori1Yuka Akagi2Tatsuya Oda3Yasuyuki S. Kida4Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, JapanCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Ibaraki, JapanCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Ibaraki, JapanDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, JapanCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Ibaraki, JapanCancer-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. Furthermore, we analyzed the metabolites in pancreatic tumor tissues in a mice model. The metabolites extracted as candidates in the in vitro experiments were also detected in the in vivo experiments. 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.https://www.mdpi.com/2072-6694/14/6/1375cancer-associated fibroblaststumor microenvironmentpancreatic cancerintracellular metabolismglycolysisoxidative phosphorylation |
| spellingShingle | Yoshihiro Miyazaki Nobuhito Mori Yuka Akagi Tatsuya Oda Yasuyuki S. Kida Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts Cancers cancer-associated fibroblasts tumor microenvironment pancreatic cancer intracellular metabolism glycolysis oxidative phosphorylation |
| title | Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts |
| title_full | Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts |
| title_fullStr | Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts |
| title_full_unstemmed | Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts |
| title_short | Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts |
| title_sort | potential metabolite markers for pancreatic cancer identified by metabolomic analysis of induced cancer associated fibroblasts |
| topic | cancer-associated fibroblasts tumor microenvironment pancreatic cancer intracellular metabolism glycolysis oxidative phosphorylation |
| url | https://www.mdpi.com/2072-6694/14/6/1375 |
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