Neuropeptide S receptor 1 (NPSR1) activates cancer-related pathways and is widely expressed in neuroendocrine tumors
| Autor: | Caj Haglund, Lilli Sundman, Ville Pulkkinen, Satu Maria Remes, Jaana Hagström, Sini Ezer, Cilla Söderhäll, Juha Kere, Johanna Arola, Dario Greco |
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| Přispěvatelé: | Clinicum, Keuhkosairauksien yksikkö, Research Programs Unit, Research Programme for Molecular Neurology, Department of Oral and Maxillofacial Diseases, Oral Pathology, Department of Pathology, Department of Surgery, II kirurgian klinikka, Haartman Institute (-2014) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Lung Neoplasms Skin Neoplasms Proliferation index Neuroendocrine tumors Receptors G-Protein-Coupled 0302 clinical medicine Neuropeptide S Antibody Specificity health care economics and organizations Gastrointestinal Neoplasms 0303 health sciences biology Antibodies Monoclonal General Medicine Middle Aged respiratory system Immunohistochemistry 3. Good health Gene Expression Regulation Neoplastic Neuroendocrine Tumors Original Article Female Signal transduction Signal Transduction Endocrine gland Adult inorganic chemicals medicine.medical_specialty education Pathology and Forensic Medicine 03 medical and health sciences Neuroendocrine tumor Internal medicine Endocrine Gland Neoplasms mental disorders Biomarkers Tumor medicine Humans Molecular Biology Aged Cell Proliferation Retrospective Studies 030304 developmental biology Neuropeptides technology industry and agriculture Cell Biology Transforming growth factor beta medicine.disease Endocrinology Neuroendocrine marker Cancer research biology.protein Synaptophysin 3111 Biomedicine 030217 neurology & neurosurgery |
| Zdroj: | Virchows Archiv |
| Popis: | Neuroendocrine tumors (NETs) arise from disseminated neuroendocrine cells and express general and specific neuroendocrine markers. Neuropeptide S receptor 1 (NPSR1) is expressed in neuroendocrine cells and its ligand neuropeptide S (NPS) affects cell proliferation. Our aim was to study whether NPS/NPSR1 could be used as a biomarker for neuroendocrine neoplasms and to identify the gene pathways affected by NPS/NPSR1. We collected a cohort of NETs comprised of 91 samples from endocrine glands, digestive tract, skin, and lung. Tumor type was validated by immunostaining of chromogranin-A and synaptophysin expression and tumor grade was analyzed by Ki-67 proliferation index. NPS and NPSR1 expression was quantified by immunohistochemistry using polyclonal antibodies against NPS and monoclonal antibodies against the amino-terminus and carboxy-terminus of NPSR1 isoform A (NPSR1-A). The effects of NPS on downstream signaling were studied in a human SH-SY5Y neuroblastoma cell line which overexpresses NPSR1-A and is of neuroendocrine origin. NPSR1 and NPS were expressed in most NET tissues, with the exception of adrenal pheochromocytomas in which NPS/NPSR1 immunoreactivity was very low. Transcriptome analysis of NPSR1-A overexpressing cells revealed that mitogen-activated protein kinase (MAPK) pathways, circadian activity, focal adhesion, transforming growth factor beta, and cytokine–cytokine interactions were the most altered gene pathways after NPS stimulation. Our results show that NETs are a source of NPS and NPSR1, and that NPS affects cancer-related pathways. Electronic supplementary material The online version of this article (doi:10.1007/s00428-014-1602-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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