Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer
Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantl...
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doaj-1a3e3dea3eae4cf08b237be88f9b91712020-11-24T22:02:44ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-05-01910.3389/fphys.2018.00456314377Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder CancerLea Weber0Lea Weber1Wolfgang A. Schulz2Stathis Philippou3Josephine Eckardt4Josephine Eckardt5Burkhard Ubrig6Michéle J. Hoffmann7Andrea Tannapfel8Benjamin Kalbe9Günter Gisselmann10Hanns Hatt11Department of Cellular Physiology, Ruhr University Bochum, Bochum, GermanyDepartment of Translational Wound Research, Witten/Herdecke University, Witten, GermanyDepartment of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Pathology and Cytology, Augusta Kliniken Bochum Hattingen, Bochum, GermanyDepartment of Cellular Physiology, Ruhr University Bochum, Bochum, GermanyInstitute for Physiology, Ruhr University Bochum, Bochum, GermanyClinic for Urology, Augusta Kliniken Bochum Hattingen, Bochum, GermanyDepartment of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyInstitute for Pathology, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular Physiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular Physiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular Physiology, Ruhr University Bochum, Bochum, GermanyOlfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.http://journal.frontiersin.org/article/10.3389/fphys.2018.00456/fullolfactory receptorbladderbladder cancerbiomarkernext generation sequencingOR10H1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lea Weber Lea Weber Wolfgang A. Schulz Stathis Philippou Josephine Eckardt Josephine Eckardt Burkhard Ubrig Michéle J. Hoffmann Andrea Tannapfel Benjamin Kalbe Günter Gisselmann Hanns Hatt |
spellingShingle |
Lea Weber Lea Weber Wolfgang A. Schulz Stathis Philippou Josephine Eckardt Josephine Eckardt Burkhard Ubrig Michéle J. Hoffmann Andrea Tannapfel Benjamin Kalbe Günter Gisselmann Hanns Hatt Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer Frontiers in Physiology olfactory receptor bladder bladder cancer biomarker next generation sequencing OR10H1 |
author_facet |
Lea Weber Lea Weber Wolfgang A. Schulz Stathis Philippou Josephine Eckardt Josephine Eckardt Burkhard Ubrig Michéle J. Hoffmann Andrea Tannapfel Benjamin Kalbe Günter Gisselmann Hanns Hatt |
author_sort |
Lea Weber |
title |
Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer |
title_short |
Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer |
title_full |
Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer |
title_fullStr |
Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer |
title_full_unstemmed |
Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer |
title_sort |
characterization of the olfactory receptor or10h1 in human urinary bladder cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2018-05-01 |
description |
Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer. |
topic |
olfactory receptor bladder bladder cancer biomarker next generation sequencing OR10H1 |
url |
http://journal.frontiersin.org/article/10.3389/fphys.2018.00456/full |
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