Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1402-y) contains supplementary material, which is available to authorized users.
Highlights
In airways, a proliferative effect is played directly by cholinergic agonists through nicotinic and muscarinic receptors activation
90 % of head and neck carcinomas are assigned to squamous cell carcinoma (HNSCC) and with over 600,000 new cases worldwide
Increasing evidence points out that several non-neural cell types are capable of expressing the range of proteins that form a non-neuronal cholinergic system i.e. the AChsynthesizing enzyme choline acetyltransferase (ChAT), nicotinic and muscarinic receptors, and the ACh-hydrolyzing enzymes acetyl- (AChE) and butyrylcholinesterase (BChE)
Summary
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. 90 % of head and neck carcinomas are assigned to squamous cell carcinoma (HNSCC) and with over 600,000 new cases worldwide. Increasing evidence points out that several non-neural cell types are capable of expressing the range of proteins that form a non-neuronal cholinergic system i.e. the AChsynthesizing enzyme choline acetyltransferase (ChAT), nicotinic (nAChR) and muscarinic (mAChR) receptors, and the ACh-hydrolyzing enzymes acetyl- (AChE) and butyrylcholinesterase (BChE) (reviewed in reference [4]). The catalytic action of AChE and BChE ensures rapid withdrawal of ACh, which, otherwise, may lead to cholinergic over-activation
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