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M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells

The role of muscarinic receptors in several diseases including cancer has recently emerged. To evaluate the hypothesis that muscarinic acetylcholine receptors may play a role in bladder cancer as well as in other tumor types, we investigated their expression in bladder tumor specimens. All examined...

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Autores principales: Pacini, Luca, De Falco, Elena, Di Bari, Maria, Coccia, Andrea, Siciliano, Camilla, Ponti, Donatella, Pastore, Antonio Luigi, Petrozza, Vincenzo, Carbone, Antonio, Tata, Ada Maria, Calogero, Antonella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2014
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622460/
https://www.ncbi.nlm.nih.gov/pubmed/25482946
http://dx.doi.org/10.4161/15384047.2014.955740
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author Pacini, Luca
De Falco, Elena
Di Bari, Maria
Coccia, Andrea
Siciliano, Camilla
Ponti, Donatella
Pastore, Antonio Luigi
Petrozza, Vincenzo
Carbone, Antonio
Tata, Ada Maria
Calogero, Antonella
author_facet Pacini, Luca
De Falco, Elena
Di Bari, Maria
Coccia, Andrea
Siciliano, Camilla
Ponti, Donatella
Pastore, Antonio Luigi
Petrozza, Vincenzo
Carbone, Antonio
Tata, Ada Maria
Calogero, Antonella
author_sort Pacini, Luca
collection PubMed
description The role of muscarinic receptors in several diseases including cancer has recently emerged. To evaluate the hypothesis that muscarinic acetylcholine receptors may play a role in bladder cancer as well as in other tumor types, we investigated their expression in bladder tumor specimens. All examined samples expressed the M1, M2 and M3 receptor subtypes. We also found that the level of M2 transcripts, but not those of M1 or M3, significantly increased with the tumor histologic grade. In view of these results, we proceeded to investigate whether the M2 agonist Arecaidine had any effect on in vitro cell growth and migration of T24 cells, a bladder tumor cell line expressing the muscarinic receptors, including the M2 subtype. We observed that Arecaidine significantly reduced T24 and 5637 cell proliferation and migration in a concentration dependent manner. The silencing of M2 receptor by siRNA in T24 and 5637 cell lines showed the inability of Arecaidine (100 μM) to inhibit cell proliferation after 48 hours, whereas the use of M1 and M3 antagonists in T24 appeared not to counteract the Arecaidine effect, suggesting that the inhibition of cell proliferation was directly dependent on M2 receptor activation. These data suggest that M2 muscarinic receptors may play a relevant role in bladder cancer and represent a new attractive therapeutic target.
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spelling pubmed-46224602015-11-10 M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells Pacini, Luca De Falco, Elena Di Bari, Maria Coccia, Andrea Siciliano, Camilla Ponti, Donatella Pastore, Antonio Luigi Petrozza, Vincenzo Carbone, Antonio Tata, Ada Maria Calogero, Antonella Cancer Biol Ther Research Paper The role of muscarinic receptors in several diseases including cancer has recently emerged. To evaluate the hypothesis that muscarinic acetylcholine receptors may play a role in bladder cancer as well as in other tumor types, we investigated their expression in bladder tumor specimens. All examined samples expressed the M1, M2 and M3 receptor subtypes. We also found that the level of M2 transcripts, but not those of M1 or M3, significantly increased with the tumor histologic grade. In view of these results, we proceeded to investigate whether the M2 agonist Arecaidine had any effect on in vitro cell growth and migration of T24 cells, a bladder tumor cell line expressing the muscarinic receptors, including the M2 subtype. We observed that Arecaidine significantly reduced T24 and 5637 cell proliferation and migration in a concentration dependent manner. The silencing of M2 receptor by siRNA in T24 and 5637 cell lines showed the inability of Arecaidine (100 μM) to inhibit cell proliferation after 48 hours, whereas the use of M1 and M3 antagonists in T24 appeared not to counteract the Arecaidine effect, suggesting that the inhibition of cell proliferation was directly dependent on M2 receptor activation. These data suggest that M2 muscarinic receptors may play a relevant role in bladder cancer and represent a new attractive therapeutic target. Taylor & Francis 2014-10-29 /pmc/articles/PMC4622460/ /pubmed/25482946 http://dx.doi.org/10.4161/15384047.2014.955740 Text en © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Research Paper
Pacini, Luca
De Falco, Elena
Di Bari, Maria
Coccia, Andrea
Siciliano, Camilla
Ponti, Donatella
Pastore, Antonio Luigi
Petrozza, Vincenzo
Carbone, Antonio
Tata, Ada Maria
Calogero, Antonella
M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
title M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
title_full M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
title_fullStr M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
title_full_unstemmed M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
title_short M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
title_sort m2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622460/
https://www.ncbi.nlm.nih.gov/pubmed/25482946
http://dx.doi.org/10.4161/15384047.2014.955740
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