Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis
Summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipoge...
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Elsevier
2025-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224027998 |
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| author | Nupur Ohri Johanna Häußler Nino Javakhishvili David Vieweg Anais Zourelidis Bogusz Trojanowicz Monika Haemmerle Irene Esposito Markus Glaß Yoshiaki Sunami Jörg Kleeff |
| author_facet | Nupur Ohri Johanna Häußler Nino Javakhishvili David Vieweg Anais Zourelidis Bogusz Trojanowicz Monika Haemmerle Irene Esposito Markus Glaß Yoshiaki Sunami Jörg Kleeff |
| author_sort | Nupur Ohri |
| collection | DOAJ |
| description | Summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipogenesis, fatty acid metabolism, and the ROS pathway. ANGPTL4, a key adipogenesis regulator, was highly expressed in fibroblasts and promoted pancreatic cancer cell proliferation and migration through paracrine signaling. Notably, cancer cell-driven paracrine signals appear to regulate ANGPTL4 expression in fibroblasts, suggesting that ANGPTL4 may act as a reciprocal factor in a feedback loop that enhances tumor progression. LAMA2, an extracellular matrix gene with reduced expression, suppressed pancreatic cancer cell migration, proliferation, and invasion. This study provides the temporal transcriptional analysis of fibroblast subtypes during early PDAC, highlighting the roles of metabolic reprogramming and ECM remodeling in shaping the tumor microenvironment and identifying potential therapeutic targets. |
| format | Article |
| id | doaj-art-7cbd1f19ad34437a8a429c5becc2a0de |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-7cbd1f19ad34437a8a429c5becc2a0de2025-08-20T02:39:38ZengElsevieriScience2589-00422025-01-0128111157210.1016/j.isci.2024.111572Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesisNupur Ohri0Johanna Häußler1Nino Javakhishvili2David Vieweg3Anais Zourelidis4Bogusz Trojanowicz5Monika Haemmerle6Irene Esposito7Markus Glaß8Yoshiaki Sunami9Jörg Kleeff10Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), GermanyDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), GermanyDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), Germany; Institute of Medical and Public Health Research, Ilia State University, Tbilisi 0162, GeorgiaDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), GermanyDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), GermanyDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), GermanyInstitute of Pathology, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06112 Halle (Saale), GermanyInstitute of Pathology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInstitute of Molecular Medicine, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanyDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), Germany; Corresponding authorDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle (Saale), GermanySummary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipogenesis, fatty acid metabolism, and the ROS pathway. ANGPTL4, a key adipogenesis regulator, was highly expressed in fibroblasts and promoted pancreatic cancer cell proliferation and migration through paracrine signaling. Notably, cancer cell-driven paracrine signals appear to regulate ANGPTL4 expression in fibroblasts, suggesting that ANGPTL4 may act as a reciprocal factor in a feedback loop that enhances tumor progression. LAMA2, an extracellular matrix gene with reduced expression, suppressed pancreatic cancer cell migration, proliferation, and invasion. This study provides the temporal transcriptional analysis of fibroblast subtypes during early PDAC, highlighting the roles of metabolic reprogramming and ECM remodeling in shaping the tumor microenvironment and identifying potential therapeutic targets.http://www.sciencedirect.com/science/article/pii/S2589004224027998Biological sciencesGeneticsCancer |
| spellingShingle | Nupur Ohri Johanna Häußler Nino Javakhishvili David Vieweg Anais Zourelidis Bogusz Trojanowicz Monika Haemmerle Irene Esposito Markus Glaß Yoshiaki Sunami Jörg Kleeff Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis iScience Biological sciences Genetics Cancer |
| title | Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis |
| title_full | Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis |
| title_fullStr | Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis |
| title_full_unstemmed | Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis |
| title_short | Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis |
| title_sort | gene expression dynamics in fibroblasts during early stage murine pancreatic carcinogenesis |
| topic | Biological sciences Genetics Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224027998 |
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