Neurotransmitters Influence the Development and Progression of Cancer

The innervation of tumor tissue creates the basis for the direct action of the nervous system on the processes taking place in the tumor microenvironment. This action of autonomic and sensory nerves innervating the tumor microenvironment is realized mainly through neurotransmitters and neuromodulators released from their nerve endings. In tumor tissue, nerve endings can form synapses on both tumor and nontumor cells. At these synapses, norepinephrine is released from sympathetic nerve endings, acetylcholine from parasympathetic nerve endings, and CGRP or substance P from sensory nerve endings. In addition to the above-mentioned primary neurotransmitters, cotransmitters are also released. An example is neuropeptide Y, which is released from sympathetic nerve endings together with norepinephrine. The released neurotransmitters and neuromodulators, by binding to the appropriate receptors of cells in the tumor microenvironment, induce a variety of molecular events related to tumorigenesis and proliferation of tumor cells as well as to metastasis formation. In addition, neurotransmitters and neuromodulators might reduce efficiency of anticancer treatment, as well (Arese et al. 2022) (Fig. 5.1).