title: M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells.
abstract: 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.
authors.affiliation: a Department of Medical-Surgical Sciences and Biotechnologies ; Sapienza University of Rome ; Latina , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pacini
authors.forename: Elena
authors.initials: E
authors.lastname: De Falco
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bari
authors.forename: Andrea
authors.initials: A
authors.lastname: Coccia
authors.forename: Camilla
authors.initials: C
authors.lastname: Siciliano
authors.forename: Donatella
authors.initials: D
authors.lastname: Ponti
authors.forename: Antonio Luigi
authors.initials: AL
authors.lastname: Pastore
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Petrozza
authors.forename: Antonio
authors.initials: A
authors.lastname: Carbone
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Tata
authors.forename: Antonella
authors.initials: A
authors.lastname: Calogero
mesh_terms: D001115:Arecoline / Q000031:analogs & derivatives / Q000494:pharmacology; D001706:Biopsy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D060787:Neoplasm Grading; D043585:Receptor, Muscarinic M2 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; C015688:arecaidine; D001115:Arecoline
keywords: 4-DAMP, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide; Abbreviations:; Arecaidine; FFPE, formalin-fixed, paraffin-embedded; M2 muscarinic receptors; T24 cell line; TCC, Transitional cell carcinoma; Transitional cell carcinoma; bladder cancer; mAChR, muscarinic acetylcholine receptor; tumor grade; urothelial cancer cells