The occurrence of prion protein in surgically resected pancreatic adenocarcinoma |
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| Affiliation: | 1. General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124, Pisa, Italy;2. Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124, Pisa, Italy;3. Division of Surgical Pathology, Department of Surgical, Medical Molecular Pathology and Critical Area, University of Pisa, 56124, Pisa, Italy;4. IRCCS Neuromed - Istituto Neurologico Mediterraneo, 86077, Pozzilli, Italy;5. EndoCAS (Center for Computer Assisted Surgery), University of Pisa, 56124, Pisa, Italy;1. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;2. Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;3. Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy;4. Department of Radiology, Institute for Technology Assessment, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;1. Department of Medicine, Laboratory of Forensic Medicine and Toxicology, Aristotle University of Thessaloniki, 54124, Greece;2. Department of Medicine, Laboratory of Medical Biology and Genetics, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece;3. Department of Pulmonology, I.M. Sechenov First Moscow State Medical University, Moscow, 119992, Russian Federation;4. Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010, Greece;5. Department of Medicine, Laboratory of Experimental Physiology, Aristotle University of Thessaloniki, 54124, Greece;6. Third Department of Surgery, "AHEPA" University Hospital, Aristotle University of Thessaloniki, 55236, Thessaloniki, Greece;1. Academic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, West Yorkshire, UK;2. Department of Palliative Medicine, University Hospital, Bonn, Germany;3. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway;4. Department of Anesthesia, Intensive Care, Pain Therapy and Palliative Care, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;5. European Palliative Care Research Center NTNU, Trondheim, Norway;6. Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK;1. Department of Molecular Cell Biology, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel;2. Department of Biological Services, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel;3. Department of Gastroenterology, Kaplan Medical Center, Rehovot 76100, Israel;4. Wolfson Hospital, Holon 58100, Israel |
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| Abstract: | ![]()
Background: Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker.MethodsSamples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker.ResultsAll cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI.ConclusionsOur work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications. |
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| Keywords: | Pancreatic ductal adenocarcinoma Prion protein Neurotropism Immunohistochemistry Western blot |
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