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. 1. The Nonneuronal Cholinergic System Organic compounds were formed at the very beginning of the earth, and acetylation of molecules is one of the most common reactions in nature. Because of this, it could be probable that acetylcholine (ACh) exists since the prebiotic period. This can be proved by the fact that ACh is present in bacteria, blue-green algae, yeast, fungi, protozoa, and primitive plants [1]. In addition to its presence in neurons, ACh is expressed in pro- and eukaryotic nonneuronal cells. Thus, ACh works as a signaling molecule in nonneuronal cells and tissues, before its neuronal function spans. For these reasons, Wessler et al. [2] have introduced the term “nonneuronal ACh” and “nonneuronal cholinergic system” (nNCS) to indicate the presence of ACh in cells independent of neurons. In turn, Grando [3] introduced the term “universal cytotransmitter”, which denotes the involvement of ACh in the regulation of basic and frequently nervous-independent cell functions like proliferation, differentiation, organization of the cytoskeleton, locomotion, secretion, ciliary activity, and local release of mediators (i.e., nitric oxide and proinflammatory cytokines). In addition, ACh is the main neurotransmitter in the neuronal cholinergic system. The latter is conformed by central and peripheral neurons. ACh is synthesized by preganglionic fibers of the sympathetic and parasympathetic autonomic nervous system and by postganglionic parasympathetic fibers. The organization of a cholinergic neuron and synapse is well known. In cholinergic neurons the synthesis of ACh occurs within the nerve terminal via choline acetyltransferase (ChAT) enzyme. ACh is accumulated in vesicles and is released by exocytosis to allow a highly effective
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