Guido von Figura1, Leonie Fahrenkrog-Petersen2, Ana Hidalgo-Sastre2, Daniel Hartmann3, Norbert Hüser3, Roland M Schmid2, Matthias Hebrok4, Nilotpal Roy4, Irene Esposito5. 1. II Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. Electronic address: gvfigura@tum.de. 2. II Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. 3. Chirurgische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. 4. Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. 5. Institute of Pathology, University Clinic Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany.
Abstract
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from different precursor lesions including the recently identified atypical flat lesions (AFL). While all precursor lesions and PDAC share ductal characteristics, there is an ongoing debate about the cellular origin of the different PDAC precursor lesions. In particular, pancreatic acinar cells have previously been shown to display a remarkable plasticity being able to undergo ductal dedifferentiation in the context of oncogenic stimuli. METHODS: Histological analyses were performed in a murine PDAC model that specifically expresses oncogenic Kras in adult pancreatic acinar cells. Occurrence, characterization, and lineage tracing of AFLs were investigated. RESULTS: Upon expression of oncogenic Kras in adult pancreatic acinar cells, AFLs with typical morphology and expression profile arise. Lineage tracing confirmed that the AFLs were of acinar origin. CONCLUSIONS: Using a murine PDAC model, this study identifies pancreatic acinar cells as a cellular source for AFLs.
OBJECTIVES:Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from different precursor lesions including the recently identified atypical flat lesions (AFL). While all precursor lesions and PDAC share ductal characteristics, there is an ongoing debate about the cellular origin of the different PDAC precursor lesions. In particular, pancreatic acinar cells have previously been shown to display a remarkable plasticity being able to undergo ductal dedifferentiation in the context of oncogenic stimuli. METHODS: Histological analyses were performed in a murinePDAC model that specifically expresses oncogenic Kras in adult pancreatic acinar cells. Occurrence, characterization, and lineage tracing of AFLs were investigated. RESULTS: Upon expression of oncogenic Kras in adult pancreatic acinar cells, AFLs with typical morphology and expression profile arise. Lineage tracing confirmed that the AFLs were of acinar origin. CONCLUSIONS: Using a murinePDAC model, this study identifies pancreatic acinar cells as a cellular source for AFLs.
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