Serotonin Receptors and Acetylcholinesterase Gene Expression Alternations: The Potential Value on Tumor Microenvironment of Gastric Cancer

Abstract

<b><i>Introduction:</i></b> Gastric cancer is one of the common causes of cancer-related death in the world. Neurotransmitters have recently been related to the proliferation of cancer cells, but the role of neurotransmitters in the progression of gastric cancer is still unexplored. The cross-talk between the nervous system and immune cells through serotonin and its receptors in the tumor microenvironment can impact tumor progress. Our purpose is to expose probable changes in serotonin receptors, acetylcholinesterase, and monoamine oxidase A gene expression in gastric cancer. <b><i>Methods:</i></b> Transcript of serotonin receptors (5-HTR2A, 5-HTR2B, 5-HTR3A, 5-HTR7) and monoamine oxidase A genes in the peripheral blood mononuclear cells (40 patients and 40 control) and tissue (21 tumors and 21 normal adjacent tissues) were assessed. The gene expression was analyzed by quantitative real-time PCR using suitable primers. Statistical analysis was performed using appropriate software (REST, Prism). <b><i>Results:</i></b> Significantly higher amounts of 5-HTR2A, 5-HTR2B, 5-HTR3A, 5-HTR7, and acetylcholinesterase gene transcripts were found in the peripheral blood of gastric cancer patients compared with healthy individuals. The expression of 5-HTR2B and 5-HTR3A genes was significantly higher (<i>p</i> = 0.0250, <i>p</i> = 0.0005, respectively) and the acetylcholinesterase gene was lower in the tissue of patients (<i>p</i> = 0.0119) compared with adjacent normal tissue. <b><i>Conclusion:</i></b> This study highlights the role of serotonin receptors in gastric cancer that might have suggestions for the development of novel therapeutics and defensive approaches that target factors associated with the link between the nervous system, cancer cells, and the tumor microenvironment.

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities

“…Elevated 5‐HT, as well as its receptors, has been demonstrated to be involved in oncogenic progression, as an potent trophic, mitogenic and anti‐apoptotic factor. 32 5‐HTRs are present in numerous types of cancer, including colorectal cancer (CRC), 19 hepatocellular carcinoma (HCC), 44 gastric cancer (GC), 45 breast cancer (BC), 46 , 47 melanoma, 48 , 49 pancreatic cancer, 50 prostate cancer (PCa), 51 , 52 , 53 lung adenocarcinoma, 54 ovarian cancer (OC), 55 bladder cancer 56 and cholangiocarcinoma 57 (Table 1 ). The intracellular reaction to 5‐HT varies between normal colon cells and CRC cells, since 5‐HT facilitated CRC cells growth without increasing the cell division rate of normal colonic crypt cells.…”