Is acetylcholine a signaling molecule for human colon cancer progression?

• Published in: Scandinavian journal of gastroenterology 2011-04, Vol.46 (4), p.446-455
• Main Authors: Novotny, Ann, Ryberg, Kristin, Heiman Ullmark, Jenny, Nilsson, Linn, Khorram-Manesh, Amir, Nordgren, Svante, Delbro, Dick S., Nylund, Gunnar
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholine - metabolism; Acetylcholinesterase - metabolism; Adult; Aged; Aged, 80 and over; alpha7 Nicotinic Acetylcholine Receptor; Antigens, Ly - metabolism; Biological and medical sciences; Biomarkers - metabolism; Biomedical Sciences; Biomedicinsk vetenskap; Blotting, Western; Cell Transformation, Neoplastic; choline acetyltransferase; Choline O-Acetyltransferase - metabolism; colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Disease Progression; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Kirurgi; Male; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN OCH HÄLSOVETENSKAP; Middle Aged; Natural Science; Naturvetenskap; Neoplasm Invasiveness; Neoplasm Staging; nicotinic acetylcholine receptor; Receptors, Nicotinic - metabolism; SLURP-1; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Tumors; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0036-5521; 1502-7708; 1502-7708
• DOI: 10.3109/00365521.2010.539252

Abstract Objective. Non-neuronal acetylcholine (ACh) has been suggested to be a mediator for the development of various types of cancer. We analyzed a possible role for this molecule in carcinogenesis and/or progression of human colon cancer, in patient biopsies harvested from the colon during surgery. We addressed whether ACh synthesis (by choline acetyltransferase) and/or degradation (by ACh esterase), as well as the expression of the α7-subtype of the nicotinic ACh receptors, and the peptide ligand at the α7 receptors, secreted mammalian Ly6/urokinase-type plasminogen activator receptor-related protein-1, respectively, are deranged in tumor tissue as compared with macroscopically tumor-free colon tissue. Methods. A total of 38 patients were grouped for analysis based on their respective Dukes stage (either Dukes A + B or C + D). A mucosal tissue sample was harvested from macroscopically tumor-free colon tissue (i.e. control tissue), as well as from the tumor, and protein lysates were prepared for quantitative Western blotting. Full-thickness specimens were taken for immunohistochemistry. Results. For all the above named markers, there was a significant difference between control and tumor tissue with regard to protein levels, and there was, in addition, a significant difference in protein levels between the Dukes A + B and C + D groups. Conclusion. The current findings may suggest a role for ACh in colon carcinogenesis/cancer progression; the data obtained could have prognostic and/or therapeutic significance for this disease.