The expression of IL-8 and IL-8 receptors in pancreatic adenocarcinomas and pancreatic neuroendocrine tumours |
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| Authors: | Farah Hussain Jayson Wang Raida Ahmed Stephanie K Guest Eric W-F Lam Gordon Stamp Mona El-Bahrawy |
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| Institution: | 1. Department of Surgery, Imperial College, London, UK;2. Department of Histopathology, Imperial College, London, UK;3. Department of Oncology, Imperial College, London, UK;1. Department for Endocrinology, Diabetes and Metabolism, University Clinical Hospital Centre “Sestre milosrdnice”, Zagreb, Croatia;2. Laboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia;3. Department for Clinical Pathology, University Clinical Hospital Centre “Sestre milosrdnice”, Zagreb, Croatia;1. Department of Anatomic Pathology, IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy;2. Roma ENETS Center of Excellence, IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy;3. Gynecological and Breast Pathology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy;4. Anatomic Pathology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy;5. Institute of Pathology, Università Cattolica-IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy;1. Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden;2. Yale University School of Medicine, New Haven CT, USA;3. Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, Netherlands;4. Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, Netherlands;5. Charite Universitätsmedzin Berlin, Berlin, Germany;6. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA;7. Imperial College London, Hammersmith Campus, London, UK;8. Division of Gastroenterology, University of Pennsylvania Health System, Philadelphia, PA, USA;9. Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA;10. H Lee Moffitt Cancer Center, Tampa, FL, USA;11. University College London Cancer Institute, London, UK;12. Brown University, Liver Research Center, Providence, RI, USA;13. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA;14. Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA;15. Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA;p. Markey Cancer Center, University of Kentucky, Lexington, KY, USA;1. Laboratorio Sperimentale di Ricerche di Neuroendocrinologia Geriatrica ed Oncologica, Istituto Auxologico Italiano IRCCS, Milan, Italy;2. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy;3. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy;4. Department of Human Pathology of Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy;5. Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy;6. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy;7. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy;1. Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK;2. Department of Diabetes and Endocrinology, Melbourne Health, Melbourne, VIC, Australia;3. Department of Diabetes and Endocrinology, Western Health, Melbourne, VIC, Australia;4. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia;5. Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK |
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| Abstract: | BackgroundInflammatory mediators influence tumour progression. IL-8 has been shown to have pro-angiogenic, mitogenic and motogenic effects and several studies have demonstrated the expression of IL-8 by various human pancreatic cancer cell lines. Methods: The expression of IL-8 and IL-8 receptors was studied in 52 pancreatic adenocarcinomas and 52 pancreatic neuroendocrine tumours using immunohistochemistry. The expression of IL-8 and IL-8 receptors was also assessed in eight pancreatic adenocarcinomas and seven neuroendocrine tumours in comparison to normal pancreatic tissue using real time quantitative PCR (qRT-PCR). Results: Immunohistochemical analysis of the expression of IL-8, IL-8RA and IL-8RB in 52 pancreatic adenocarcinomas demonstrated expression in 25%, 75% and 79% of pancreatic adenocarcinomas, respectively. There was no statistically significant correlation between expression and tumour grade and stage for any of the three antigens. IL-8, IL-8RA and IL-8RB expression was detected in 21%, 63% and 92% of 52 pancreatic neuroendocrine tumours. There was no statistically significant correlation between expression and tumour grade for any of the three antigens. Using qRT-PCR, the expression of each of IL-8, IL-8RA and IL-8RB mRNA was increased in 75% of pancreatic adenocarcinomas. IL-8, IL-8RA and IL-8RB mRNA expression was also increased in 57%, 43% and 29% of pancreatic neuroendocrine tumours. Quantitatively, there was a significant increase in expression level of IL-8 in tumours of both types in comparison to normal pancreatic tissue (38.5-fold in adenocarcinomas and 43.9-fold in neuroendocrine tumours). There was also increased expression of IL-8RA in both tumour types, with higher levels in adenocarcinomas, 2.7-fold and neuroendocrine tumours, 1.7-fold. IL-8RB was slightly increased in adenocarcinomas in comparison to normal pancreas (1.4-fold), but the expression was decreased in neuroendocrine tumours compared with normal pancreas (0.9-fold). Conclusion: This is the first study to show that IL-8 and IL-8 receptors are upregulated in both pancreatic adenocarcinomas and neuroendocrine tumours, and indicate this signalling pathway may modulate tumour behaviour through autocrine and/or paracrine loops. |
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