Nicotine, the main addictive substance in tobacco, is known to play a role in the development and/or progression of a number of malignant tumors. However, nicotine's involvement in the pathogenesis of cholangiocarcinoma is controversial. Therefore, we studied the effects of nicotine on the growth of cholangiocarcinoma cells in vitro and the progression of cholangiocarcinoma in a mouse xenograft model. The predominant subunit responsible for nicotine-mediated proliferation in normal and cancer cells, the α7 nicotinic acetylcholine receptor (α7-nAChR), was more highly expressed in human cholangiocarcinoma cell lines compared with normal human cholangiocytes. Nicotine also stimulated the proliferation of cholangiocarcinoma cell lines and promoted α7-nAChR–dependent activation of proliferation and phosphorylation of extracellular-regulated kinase in Mz-ChA-1 cells. In addition, nicotine and PNU282987 (α7-nAChR agonist) accelerated the growth of the cholangiocarcinoma tumors in our xenograft mouse model and increased fibrosis, proliferation of the tumor cells, and phosphorylation of extracellular-regulated kinase activation. Finally, α7-nAChR was expressed at significantly higher levels in human cholangiocarcinoma compared with normal human control liver samples. Taken together, results of this study suggest that nicotine acts through α7-nAChR and plays a novel role in the pathogenesis of cholangiocarcinoma. Furthermore, nicotine may act as a mitogen in cholestatic liver disease processes, thereby facilitating malignant transformation.

Martã­nez, A., Jensen, K., Hall, C., O'Brien, A., Ehrlich, L., White, T., et al. (2017). Nicotine Promotes Cholangiocarcinoma Growth in Xenograft Mice. THE AMERICAN JOURNAL OF PATHOLOGY, 187(5), 1093-1105 [10.1016/j.ajpath.2017.01.011].

Nicotine Promotes Cholangiocarcinoma Growth in Xenograft Mice

BERNUZZI, FRANCESCA VERONICA;INVERNIZZI, PIETRO;
2017

Abstract

Nicotine, the main addictive substance in tobacco, is known to play a role in the development and/or progression of a number of malignant tumors. However, nicotine's involvement in the pathogenesis of cholangiocarcinoma is controversial. Therefore, we studied the effects of nicotine on the growth of cholangiocarcinoma cells in vitro and the progression of cholangiocarcinoma in a mouse xenograft model. The predominant subunit responsible for nicotine-mediated proliferation in normal and cancer cells, the α7 nicotinic acetylcholine receptor (α7-nAChR), was more highly expressed in human cholangiocarcinoma cell lines compared with normal human cholangiocytes. Nicotine also stimulated the proliferation of cholangiocarcinoma cell lines and promoted α7-nAChR–dependent activation of proliferation and phosphorylation of extracellular-regulated kinase in Mz-ChA-1 cells. In addition, nicotine and PNU282987 (α7-nAChR agonist) accelerated the growth of the cholangiocarcinoma tumors in our xenograft mouse model and increased fibrosis, proliferation of the tumor cells, and phosphorylation of extracellular-regulated kinase activation. Finally, α7-nAChR was expressed at significantly higher levels in human cholangiocarcinoma compared with normal human control liver samples. Taken together, results of this study suggest that nicotine acts through α7-nAChR and plays a novel role in the pathogenesis of cholangiocarcinoma. Furthermore, nicotine may act as a mitogen in cholestatic liver disease processes, thereby facilitating malignant transformation.
Articolo in rivista - Articolo scientifico
Aged; Animals; Bile Duct Neoplasms; Cell Line, Tumor; Cell Proliferation; Cholangiocarcinoma; Extracellular Signal-Regulated MAP Kinases; Female; Fibrosis; Heterografts; Humans; Keratin-19; MAP Kinase Signaling System; Male; Mice; Middle Aged; Neoplasm Transplantation; Nicotine; Nicotinic Agonists; S100 Calcium-Binding Protein A4; alpha7 Nicotinic Acetylcholine Receptor; 2734
English
2017
187
5
1093
1105
open
Martã­nez, A., Jensen, K., Hall, C., O'Brien, A., Ehrlich, L., White, T., et al. (2017). Nicotine Promotes Cholangiocarcinoma Growth in Xenograft Mice. THE AMERICAN JOURNAL OF PATHOLOGY, 187(5), 1093-1105 [10.1016/j.ajpath.2017.01.011].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/174277
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