Cancer-associated differences in acetylcholinesterase activity in bronchial aspirates from patients with lung cancer

Abstract

In non-neuronal contexts, ACh (acetylcholine) is thought to be involved in the regulation of vital cell functions, such as proliferation, differentiation, apoptosis and cell-cell interaction. In airways, most cells express the non-neuronal cholinergic system, each containing a specific set of components required for synthesis, signal transduction and ACh hydrolysis. The aim of the present study was determine the expression of cholinergic system components in bronchial aspirates from control subjects and patients with lung cancer. We conducted an analysis of cholinergic components in the stored soluble and cellular fraction of bronchial aspirates from non-cancerous patients and patients diagnosed with lung cancer. The results show that the fluid secreted by human lung cells contains enough AChE (acetylcholinesterase) activity to control ACh levels. Thus these findings demonstrate that: (i) AChE activity is significantly lower in aspirates from squamous cell carcinomas; (ii) the molecular distribution of AChE in both bronchial cells and fluids consisted of amphiphilic monomers and dimers; and (iii) choline acetyltransferase, nicotinic receptors and cholinesterases are expressed in cultured human lung cells, as demonstrated by RT-PCR (reverse transcriptase-PCR). It appears that the non-neuronal cholinergic system is involved in lung physiology and lung cancer. The physiological consequences of the presence of non-neuronal ACh will depend on the particular cholinergic signalling network in each cell type. Clarifying the pathophysiological actions of ACh remains an essential task and warrants further investigation.

Expression of cholinesterases in human kidney and its variation in renal cell carcinoma types

“…1C), meningioma [37], breast [36], and colon [30], and the observation of butyrylcholinesterase mRNA in kidney (Fig. 4), colon [30], and cancerous cell lines [39], support the idea of butyrylcholinesterase synthesis in the organs themselves. Nevertheless, the great quantity of butyrylcholinesterase activity in blood plasma [40] might lead us to think that renal butyrylcholinesterase arises totally or in part from blood.…”

“…The presence of acetylcholinesterase‐T mRNA in kidney (Fig. 4) contrasts with the absence of catalytic acetylcholinesterase‐T protein from kidney and cancerous cell lines of lung, breast, and gut [39], a feature that might be attributed to microRNA‐induced translational repression of the acetylcholinesterase‐T mRNA in epithelial cells. In this respect, there is evidence of a regulatory role for microRNA‐132 in the expression of acetylcholinesterase in leukocytes [44], but other reasons may exist, e.g.…”

Muscarinic Receptor Agonists and Antagonists: Effects on Cancer

“…Martinez-Moreno has similarly reported that cholinesterase levels are reduced in lung cancer, thus increasing the available ACh to stimulate tumor growth (de Martinez-Lopez et al 2008; Martinez-Moreno et al 2006). …”

Cell transformation assays for prediction of carcinogenic potential: state of the science and future research needs

“…Several lines of evidence suggest that cholinesterases may be involved in tumour development: AChE and BChE are believed to play a role in cell proliferation and differentiation (37), cholinesterase genes have been found to be structurally altered or their products aberrantly expressed in tumours from a variety of tissues (38–40) and AChE has been shown to support anchorage-independent growth of tumour cells in vitro (41). Ectopic alkaline phosphatase expression has been found in tumours of the lung, testis, fallopian tube and gastrointestinal tract (42).…”