Is acetylcholine a signaling molecule for human colon cancer progression?

Authors: Novotny, Ann1; Ryberg, Kristin2; Heiman Ullmark, Jenny3; Nilsson, Linn4; Khorram-Manesh, Amir5; Nordgren, Svante1; Delbro, Dick S.1; Nylund, Gunnar6

Source: Scandinavian Journal of Gastroenterology, Volume 46, Number 4, April 2011 , pp. 446-455(10)

Publisher: Informa Healthcare

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Abstract:

<title>Abstract</title>

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 αα7-subtype of the nicotinic ACh receptors, and the peptide ligand at the αα7 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.

Keywords: Acetylcholine; choline acetyltransferase; colon cancer; nicotinic acetylcholine receptor; SLURP-1

Document Type: Research article

DOI: http://dx.doi.org/10.3109/00365521.2010.539252

Affiliations: 1: 1Department of Surgery, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden 2: 2Department of Chemistry and Biomedical Sciences, Karlstad University, Karlstad, Sweden 3: 3Department of Surgery, Kungäälv District Hospital, Kungäälv, Sweden 4: 4Department of Surgery, Vääxjöö Central Hospital, Vääxjöö, Sweden 5: 5Prehospital and Disaster Medicine Centre, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden 6: 6Department of Surgery, Söödra ÄÄlvsborg's Hospital, Boråås, Sweden

Publication date: 2011-04-01

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