Is acetylcholine a signaling molecule for human colon cancer progression?
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.


CONCLUSIONS
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.
Department of Surgery, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Ann
A
Novotny
Kristin
K
Ryberg
Jenny
J
Heiman Ullmark
Linn
L
Nilsson
Amir
A
Khorram-Manesh
Svante
S
Nordgren
Dick S
DS
Delbro
Gunnar
G
Nylund
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000950:Antigens, Ly / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000950:Antigens, Ly; D015415:Biomarkers; C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; C048963:SLURP1 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D014568:Urokinase-Type Plasminogen Activator; D000109:Acetylcholine