RRC ID 54093
Author Nguyen PH, Touchefeu Y, Durand T, Aubert P, Duchalais E, Bruley des Varannes S, Varon C, Neunlist M, Matysiak-Budnik T.
Title Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type.
Journal Tumour Biol.
Abstract Gastric cancer is the third leading cause of cancer-related death worldwide, but the mechanisms of gastric carcinogenesis are not completely understood. Recently, the role of cholinergic neuronal pathways in promoting this process has been demonstrated. Our aim was to extend these studies and to evaluate, using an in vitro model of tumorspheres, the effect of acetylcholine on human gastric cancer cells, and the role of acetylcholine receptors and of the nitric oxide pathway, in this effect. The gastric cancer cell line MKN-45 of the diffuse type of gastric cancer was cultured in the presence of acetylcholine, or different agonists or inhibitors of muscarinic and nicotinic acetylcholine receptors, or nitric oxide donor or inhibitor of the nitric oxide pathway, and the number and size of tumorspheres were assessed. The expression of cancer stem cell markers (CD44 and aldehyde dehydrogenase) was also evaluated by immunofluorescence and quantitative reverse transcription polymerase chain reaction. We showed that acetylcholine increased both the number and size of tumorspheres and that this effect was reproduced with both muscarinic and nicotinic acetylcholine receptors agonists and was inhibited by both receptor antagonists. The nitric oxide donor stimulated the tumorsphere formation, while the nitric oxide synthesis inhibitor inhibited the stimulatory effect of acetylcholine. Moreover, acetylcholine increased the expression of stem cell markers on gastric cancer cells. These results indicate that acetylcholine induces the stem cell properties of gastric cancer cells and both muscarinic and nicotinic receptors and a nitrergic pathway might be involved in this effect.
Volume 40(9)
Pages 1010428318799028
Published 2018-9
DOI 10.1177/1010428318799028
PMID 30207200
MeSH Acetylcholine / metabolism* Biomarkers, Tumor / metabolism Cell Line, Tumor Humans Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / pathology* Nicotinic Agonists / pharmacology Nitric Oxide / metabolism Nitric Oxide Donors / pharmacology Receptors, Cholinergic / metabolism Receptors, Nicotinic / metabolism Signal Transduction / drug effects Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology*
Resource
Human and Animal Cells MKN45(RCB1001)