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The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine

The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian...

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Autores principales: Deuster, Eileen, Hysenaj, Ivi, Kahaly, Maja, Schmoeckel, Elisa, Mayr, Doris, Beyer, Susanne, Kolben, Thomas, Hester, Anna, Kraus, Fabian, Chelariu-Raicu, Anca, Burges, Alexander, Mahner, Sven, Jeschke, Udo, Trillsch, Fabian, Czogalla, Bastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466210/
https://www.ncbi.nlm.nih.gov/pubmed/34571986
http://dx.doi.org/10.3390/cells10092337
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author Deuster, Eileen
Hysenaj, Ivi
Kahaly, Maja
Schmoeckel, Elisa
Mayr, Doris
Beyer, Susanne
Kolben, Thomas
Hester, Anna
Kraus, Fabian
Chelariu-Raicu, Anca
Burges, Alexander
Mahner, Sven
Jeschke, Udo
Trillsch, Fabian
Czogalla, Bastian
author_facet Deuster, Eileen
Hysenaj, Ivi
Kahaly, Maja
Schmoeckel, Elisa
Mayr, Doris
Beyer, Susanne
Kolben, Thomas
Hester, Anna
Kraus, Fabian
Chelariu-Raicu, Anca
Burges, Alexander
Mahner, Sven
Jeschke, Udo
Trillsch, Fabian
Czogalla, Bastian
author_sort Deuster, Eileen
collection PubMed
description The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients.
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spelling pubmed-84662102021-09-27 The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine Deuster, Eileen Hysenaj, Ivi Kahaly, Maja Schmoeckel, Elisa Mayr, Doris Beyer, Susanne Kolben, Thomas Hester, Anna Kraus, Fabian Chelariu-Raicu, Anca Burges, Alexander Mahner, Sven Jeschke, Udo Trillsch, Fabian Czogalla, Bastian Cells Article The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients. MDPI 2021-09-07 /pmc/articles/PMC8466210/ /pubmed/34571986 http://dx.doi.org/10.3390/cells10092337 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Deuster, Eileen
Hysenaj, Ivi
Kahaly, Maja
Schmoeckel, Elisa
Mayr, Doris
Beyer, Susanne
Kolben, Thomas
Hester, Anna
Kraus, Fabian
Chelariu-Raicu, Anca
Burges, Alexander
Mahner, Sven
Jeschke, Udo
Trillsch, Fabian
Czogalla, Bastian
The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine
title The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine
title_full The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine
title_fullStr The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine
title_full_unstemmed The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine
title_short The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine
title_sort platelet-activating factor receptor’s association with the outcome of ovarian cancer patients and its experimental inhibition by rupatadine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466210/
https://www.ncbi.nlm.nih.gov/pubmed/34571986
http://dx.doi.org/10.3390/cells10092337
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