Muscarinic acetylcholine receptor M3 in proliferation and perineural invasion of cholangiocarcinoma cells.
BACKGROUND
Cholangiocarcinoma, a type of malignant tumor, originates from epithelial cells of the bile duct. Perineural invasion is common path for cholangiocarcinoma metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It has been reported that muscarinic acetylcholine receptor M3 (mAChR M3) is widely expressed in digestive tract cancer, and may play an important role in the proliferation, differentiation, transformation and carcinogenesis of tumors. This study was to explore the effect of mAChR M3 on the growth of cholangiocarcinoma cells in vitro and provide a new approach to the pathogenesis and treatment of cholangiocarcinoma.


METHODS
Streptavidin-biotin complex immunohistochemistry was carried out to assess the expression of mAChR M3 in surgical specimens of cholangiocarcinomas (40 cases) and normal bile duct tissues (9), as well as to investigate nerve infiltration. The cholangiocarcinoma cells were treated with different concentrations of selective M-receptor agonist pilocarpine and M-receptor blocker atropine sulfate to induce changes in cell proliferation. The experimental data were analyzed by the Chi-square test.


RESULTS
The strongly-positive expression rate of mAChR M3 was much higher in poorly-differentiated (69%, 9/13) than in well- and moderately-differentiated cholangiocarcinomas (30%, 8/27) (X2=5.631, P<0.05). The strongly-positive mAChR M3 expression rate in hilar cholangiocarcinoma (50%, 14/28) was higher than that in cholangiocarcinomas from the middle and lower common bile duct (25%, 3/12) (X2=2.148, P<0.05). Cholangiocarcinomas with distant metastasis had a strongly-positive expression rate (75%, 9/12), which was much higher than those without distant metastasis (29%, 8/28) (X2=7.410, P<0.01). The absorbance value in the pilocarpine+atropine group was significantly higher than the corresponding value in the pilocarpine group.


CONCLUSIONS
The expression of mAChR M3 is influenced by the extent of differentiation, distant metastasis and the site of cholangiocarcinoma. It also plays a key role in the proliferation and metastasis of cholangiocarcinoma.
Second Department of General Surgery, Affiliated Medical College Hospital, Qingdao University, Qingdao 266003, China.
Yu-Jie
YJ
Feng
Bing-Yuan
BY
Zhang
Ru-Yong
RY
Yao
Yun
Y
Lu
D001285:Atropine / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016009:Chi-Square Distribution; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010525:Peripheral Nerves / Q000473:pathology*; D010862:Pilocarpine / Q000494:pharmacology; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000378:metabolism*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D010862:Pilocarpine; D001285:Atropine