Dysregulated cholinergic network as a novel biomarker of poor prognostic in patients with head and neck squamous cell carcinoma

BMC Cancer

Research Article

María Fernanda Montenegro¹  José Neptuno Rodríguez-López¹  Cecilio J Vidal¹  Susana Nieto-Cerón²  María Fuensanta López-Moreno²  Ana Cristina Castillo-González²  José Antonio Noguera²  Juan Cabezas-Herrera²  Diego Hellín-Meseguer³  Juan Pablo Pelegrín-Hernández³ 

[1] Department of Biochemistry and Molecular Biology A, School of Biology, Regional Campus of International Excellence “Campus Mare Nostrum”, IMIB-University of Murcia, 30100, Murcia, Spain;Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, 30120, Murcia, Spain;Otorhinolaryngology Surgical Service, University Hospital Virgen de la Arrixaca IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, 30120, Murcia, Spain;

关键词: Cholinergic system;    Non-neuronal compartment;    Human airways;    Head and neck cancer;   

DOI  :  10.1186/s12885-015-1402-y

 received in 2014-09-29, accepted in 2015-04-29,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIn airways, a proliferative effect is played directly by cholinergic agonists through nicotinic and muscarinic receptors activation. How tumors respond to aberrantly activated cholinergic signalling is a key question in smoking-related cancer. This research was addressed to explore a possible link of cholinergic signalling changes with cancer biology.MethodsFifty-seven paired pieces of head and neck squamous cell carcinoma (HNSCC) and adjacent non-cancerous tissue (ANCT) were compared for their mRNA levels for ACh-related proteins and ACh-hydrolyzing activity.ResultsThe measurement in ANCT of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (5.416 ± 0.501 mU/mg protein and 6.350 ± 0.599 mU/mg protein, respectively) demonstrated that upper respiratory tract is capable of controlling the availability of ACh. In HNSCC, AChE and BChE activities dropped to 3.584 ± 0.599 mU/mg protein (p = 0.002) and 3.965 ± 0.423 mU/mg protein (p < 0.001). Moreover, tumours with low AChE activity and high BChE activity were associated with shorter patient overall survival. ANCT and HNSCC differed in mRNA levels for AChE-T, α3, α5, α9 and β2 for nAChR subunits. Tobacco exposure had a great impact on the expression of both AChE-H and AChE-T mRNAs. Unaffected and cancerous pieces contained principal AChE dimers and BChE tetramers. The lack of nerve-born PRiMA-linked AChE agreed with pathological findings on nerve terminal remodelling and loss in HNSCC.ConclusionsOur results suggest that the low AChE activity in HNSCC can be used to predict survival in patients with head and neck cancer. So, the ChE activity level can be used as a reliable prognostic marker.

【 授权许可】

Unknown   
© Castillo-González et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.