Abstract
Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.
Highlights
Organic compounds were formed at the very beginning of the earth, and acetylation of molecules is one of the most common reactions in nature
In cholinergic neurons the synthesis of ACh occurs within the nerve terminal via choline acetyltransferase (ChAT) enzyme
Previous studies performed in placenta indicate that the release of ACh in nonneuronal cells is mediated by the family of organic cation transporters (OCT) [5]
Summary
Organic compounds were formed at the very beginning of the earth, and acetylation of molecules is one of the most common reactions in nature. The analysis of 28 squamous cell lung carcinomas showed increased levels of both α5 and β3 nAChRs mRNA and ACh which were associated with increased levels of ChAT and decreased amounts of AChE mRNAs. cholinergic signaling is broadly increased in this type of tumor due to the high levels of expression of both receptors and ligands [16]. We found that mAChRs are constitutively expressed in three different cell lines LM2, LM3, and LMM3 derived from murine mammary adenocarcinomas that spontaneously arose in BALB/c mice Stimulation of these functional receptors potentiates different stages of tumorigenesis, such as cell proliferation, migration, angiogenesis, and tumor growth in vivo [26,27,28]. Our results indicate that human monocytederived DCs express M3, M4, and M5 receptors as well as ChAT and AChE in both immature and mature DCs [40]
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