The role of neural-related factors in the metastasis of the gastrointestinal cancer

Neurotransmitters are identified to be endogenous chemicals and act on neurons to transmit signals to each other or to a target cell across synapse. They are involved in many brain functions including analgesia, reward, food intake, metabolism, reproduction, social behaviors, learning, and memory. Recently, sympathetic nerve fibers were detected in many solid tumors including gastrointestinal cancer, supporting the idea that neural system has effects on tumor progression. Neurotransmitters were secreted from the sympathetic nerve fibers and subsequently infiltrated into tumor tissues. Further studies disclosed the different mechanisms of various kinds of neurotransmitters in the progression of carcinogenesis, including tumor cell proliferation, angiogenesis, and tumor invasion and metastasis. Neurotransmitters are mainly subdivided into four types, amino acids, monoamines, peptides, and others, each of which contains multiple chemicals. For this reason, we cannot describe each in detail. In this review, we will focus on several important neurotransmitters including tachykinis, neuropeptide Y, and b-adrenergic receptors. How they function and their crosstalks with the immune system in the progression, especially the metastasis of gastrointestinal cancer, will be described. Finally, we will summarize the clinical implications in the treatment of gastrointestinal cancer.