Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells |
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| Affiliation: | 1. INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France;2. Normandy University, Normandy, France;3. Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, Faculty of Sciences Dhar-El Mahraz, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco;4. Department of Pathology, University Hospital Hassan II, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco;1. Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China;2. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210002, China;1. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland;2. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland;3. Department of Oncology, Hôpital Saint-Antoine, Paris, France;4. University Pierre et Marie Curie, Paris VI, Paris, France;5. University of Helsinki, Helsinki, Finland;6. STAT-Consulting, Nokia, Finland;7. International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium;1. Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Japan;2. Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Japan;3. Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Japan;4. Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan;1. Department of Gynaecology and Obstetrics, University Ulm, Prittwitzstraße 43, 89075 Ulm, Germany;2. Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 69, 55131 Mainz, Germany;3. Department of economics, Institute for medical biostistics, epidemiology and informatics, University medical centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 69, Mainz, Germany;1. Institute of Pathology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany;2. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany;3. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany;4. Tissue Bank of the National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany;5. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer 581, 69120 Heidelberg, Germany;6. Institute of Pathology, SLK-Clinics Heilbronn, Am Gesundbrunnen 20-26, 74078 Heilbronn, Germany;1. Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;2. Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;3. Medical Oncology Unit ‘Sandro Pitigliani’, S. Stefano Civil Hospital, Prato, Italy;4. Medical Oncology, IRCCS – Istituto di Candiolo, Candiolo, Italy;5. Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy;6. Department of Oncology, University Hospital of Palermo, Palermo, Italy;7. Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;8. Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy;9. Pharmacy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;10. Melanoma and Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;11. Melanoma and Sarcoma, Surgery Department, Istituto Europeo di Oncologia, Milan, Italy;12. Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy |
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| Abstract: | AimIn prostate cancer (PCa), neuroendocrine differentiation (NED) is commonly observed in relapsing, hormone therapy-resistant tumours after androgen deprivation. However, the molecular mechanisms involved in the NED of PCa cells remain poorly understood. In this study, we investigated the expression of the neuroendocrine secretory protein secretogranin II (SgII) in PCa, and its potential involvement in the progression of this cancer as a granulogenic factor promoting NED.MethodsWe have examined SgII immunoreactivity in 25 benign prostate hyperplasia and 32 PCa biopsies. In vitro experiments were performed to investigate the involvement of SgII in the neuroendocrine differentiation and the proliferation of PCa cell lines.ResultsWe showed that immunoreactive SgII intensity correlates with tumour grade in PCa patients. Using the androgen-dependent lymph node cancer prostate cells (LNCaP) cells, we found that NED triggered by androgen deprivation is associated with the induction of SgII expression. In addition, forced expression of SgII in LNCaP cells implemented a regulated secretory pathway by triggering the formation of secretory granule-like structures competent for hormone storage and regulated release. Finally, we found that SgII promotes prostate cancer (CaP) cell proliferation.ConclusionThe present data show that SgII is highly expressed in advanced PCa and may contribute to the neuroendocrine differentiation by promoting the formation of secretory granules and the proliferation of PCa cells. |
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| Keywords: | Secretogranin Secretory granule Neuroendocrine differentiation Prostate cancer |
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