Is acetylcholine a signaling molecule for human colon cancer progression?

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.

Key Words::

• Acetylcholine
• choline acetyltransferase
• colon cancer
• nicotinic acetylcholine receptor
• SLURP-1

Acknowledgements

The authors are grateful to Drs. F. Aldenborg, H.-A. Hansson, R. Hultborn and B.-M. Iresjö, for invaluable advice and suggestions. Source of financial support: the Anna-Lisa and Bror Björnsson Foundation (D.S. Delbro; A. Novotny), the Borås Research and Development Foundation Against Cancer (G. Nylund), the Gothenburg Medical Society (A. Khorram-Manesh, G. Nylund), the LUA-ALF agreement (S. Nordgren, D.S. Delbro), Linnaeus University (formerly the University of Kalmar; D.S. Delbro, A. Novotny), Karlstad University (D.S. Delbro) and the Västra Götalandregionen (G. Nylund).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.