Top

Published in:

01-09-2011 | Translational Research and Biomarkers

Nicotine Promotes Cell Migration Through Alpha7 Nicotinic Acetylcholine Receptor in Gastric Cancer Cells

Authors: Yung-Chang Lien, MD, Weu Wang, MD, Li-Jen Kuo, MD, Jun-Jen Liu, PhD, Po-Li Wei, MD, PhD, Yuan-Soon Ho, PhD, Wen-Chien Ting, MD, Chih-Hsiung Wu, MD, PhD, Yu-Jia Chang, PhD

Published in: Annals of Surgical Oncology | Issue 9/2011

Abstract

Background

The objective was to study the mechanism of nicotine-enhanced migration of gastric cancer cells. Long-term cigarette smoking increases the risk of gastric cancer mortality. Tobacco-specific mitogen, nicotine, was reported to correlate with cancer progression on gastric cancer. Since metastasis is the major cause of cancer death, the influence of nicotine on the migration of gastric cancer cells remains to be determined.

Materials and Methods

The influence of nicotine on migration of gastric cancer cells was evaluated by transwell assay and wound-healing migration assay. Receptor-mediated migration was studied by both inhibitor and small interfering RNA.

Results

Alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in gastric cancer cell lines, AGS cells. Nicotine enhanced AGS cell migration in transwell assay and wound-healing migration assay in a dose-dependent manner. We used inhibitor and siRNA to demonstrate that alpha7-nAChR mediated nicotine-enhanced gastric cancer cell migration through downregulation E-cadherin and upregulation ZEB-1 and snail.

Conclusions

Tobacco-specific mitogen, nicotine, enhanced gastric cancer metastasis through alpha7-nAChR and suppression of E-cadherin level—one of the hallmarks of epithelial to mesenchymal transition. Therefore, patients with gastric cancer should avoid smoking.

Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009;472:467–77.PubMedCrossRef

NIH State-of-the-Science conference statement on tobacco use: prevention, cessation, and control. NIH Consens State Sci Statements. 2006;23:1–26.

Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 2003;3:733–44.PubMedCrossRef

Tsurutani J, Castillo SS, Brognard J, et al. Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis. 2005;26:1182–95.PubMedCrossRef

Dasgupta P, Chellappan SP. Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story. Cell Cycle. 2006;5:2324–8.PubMedCrossRef

Zheng Y, Ritzenthaler JD, Roman J, Han S. Nicotine stimulates human lung cancer cell growth by inducing fibronectin expression. Am J Respir Cell Mol Biol. 2007;37:681–90.PubMedCrossRef

Chowdhury P, Udupa KB. Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation. World J Gastroenterol. 2006;12:7428–32.PubMed

Chen RJ, Ho YS, Guo HR, Wang YJ. Rapid activation of Stat3 and ERK1/2 by nicotine modulates cell proliferation in human bladder cancer cells. Toxicol Sci. 2008;104:283–93.PubMedCrossRef

Wong HP, Yu L, Lam EK, et al. Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation. Toxicol Sci. 2007;97:279–87.PubMedCrossRef

10.

Shin VY, Wu WK, Ye YN, et al. Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2. Carcinogenesis. 2004;25:2487–95.PubMedCrossRef

11.

Shin VY, Jin HC, Ng EK, et al. Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and beta-adrenergic receptor signaling pathways. Toxicol Appl Pharmacol. 2008;233:254–61.PubMedCrossRef

12.

Schuller HM. Nitrosamines as nicotinic receptor ligands. Life Sci. 2007;80:2274–80.PubMedCrossRef

13.

Egleton RD, Brown KC, Dasgupta P. Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis. Trends Pharmacol Sci. 2008;29:151–8.PubMedCrossRef

14.

Wei PL, Chang YJ, Ho YS, et al. Tobacco-specific carcinogen enhances colon cancer cell migration through alpha7-nicotinic acetylcholine receptor. Ann Surg. 2009;249:978–85.PubMedCrossRef

15.

Xu L, Deng X. Protein kinase Ciota promotes nicotine-induced migration and invasion of cancer cells via phosphorylation of micro- and m-calpains. J Biol Chem. 2006;281:4457–66.PubMedCrossRef

16.

Guo J, Ibaragi S, Zhu T, et al. Nicotine promotes mammary tumor migration via a signaling cascade involving protein kinase C and CDC42. Cancer Res. 2008;68:8473–81.PubMedCrossRef

17.

Plate K. From angiogenesis to lymphangiogenesis. Nat Med. 2001;7:151–2.PubMedCrossRef

18.

Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003;3:362–74.PubMedCrossRef

19.

Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004;4:118–32.PubMedCrossRef

20.

Perez-Moreno M, Jamora C, Fuchs E. Sticky business: orchestrating cellular signals at adherens junctions. Cell. 2003;112:535–48.PubMedCrossRef

21.

Leal MF, Lima EM, Silva PN, et al. Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil. World J Gastroenterol. 2007;13:2568–74.PubMed

22.

Wang L, Zhang F, Wu PP, et al. Disordered beta-catenin expression and E-cadherin/CDH1 promoter methylation in gastric carcinoma. World J Gastroenterol. 2006;12:4228–31.PubMed

23.

Poplawski T, Tomaszewska K, Galicki M, et al. Promoter methylation of cancer-related genes in gastric carcinoma. Exp Oncol. 2008;30:112–6.PubMed

24.

Zhang Q, Tang X, Zhang ZF, et al. Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways. Clin Cancer Res. 2007;13:4686–94.PubMedCrossRef

25.

Dasgupta P, Rizwani W, Pillai S, et al. Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer. 2009;124:36–45.PubMedCrossRef

26.

Shin VY, Wu WK, Chu KM, et al. Nicotine induces cyclooxygenase-2 and vascular endothelial growth factor receptor-2 in association with tumor-associated invasion and angiogenesis in gastric cancer. Mol Cancer Res. 2005;3:607–15.PubMedCrossRef

27.

Lawson GM, Hurt RD, Dale LC, et al. Application of urine nicotine and cotinine excretion rates to assessment of nicotine replacement in light, moderate, and heavy smokers undergoing transdermal therapy. J Clin Pharmacol. 1998;38:510–6.PubMed

28.

Wang SK, Liang PH, Astronomo RD, et al. Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc Natl Acad Sci USA. 2008;105:3690–5.PubMedCrossRef

29.

Sowinski S, Jolly C, Berninghausen O, et al. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol. 2008;10:211–9.PubMedCrossRef

30.

Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.

31.

Lauren PA, Nevalainen TJ. Epidemiology of intestinal and diffuse types of gastric carcinoma. A time-trend study in Finland with comparison between studies from high- and low-risk areas. Cancer. 1993;71:2926–33.

32.

Becker KF, Atkinson MJ, Reich U, et al. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 1994;54:3845–52.PubMed

33.

Grady WM, Willis J, Guilford PJ, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26:16–7.PubMedCrossRef

34.

Rosivatz E, Becker I, Specht K, et al. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol. 2002;161:1881–91.PubMedCrossRef

35.

Castro Alves C, Rosivatz E, Schott C, et al. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. J Pathol. 2007;211:507–15.PubMedCrossRef

36.

Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7:415–28.PubMedCrossRef

37.

Shin VY, Jin HC, Ng EK, et al. Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth. Cancer Lett. 2010;292:237–45.PubMedCrossRef

38.

Solinas M, Scherma M, Fattore L, et al. Nicotinic alpha 7 receptors as a new target for treatment of cannabis abuse. J Neurosci. 2007;27:5615–20.PubMedCrossRef

39.

Shao XM, Feldman JL. Central cholinergic regulation of respiration: nicotinic receptors. Acta Pharmacol Sin. 2009;30:761–70.PubMedCrossRef

40.

Benowitz NL. Nicotine addiction. N Engl J Med. 2010;362:2295–303.PubMedCrossRef

Title: Nicotine Promotes Cell Migration Through Alpha7 Nicotinic Acetylcholine Receptor in Gastric Cancer Cells
Authors: Yung-Chang Lien, MD
Weu Wang, MD
Li-Jen Kuo, MD
Jun-Jen Liu, PhD
Po-Li Wei, MD, PhD
Yuan-Soon Ho, PhD
Wen-Chien Ting, MD
Chih-Hsiung Wu, MD, PhD
Yu-Jia Chang, PhD
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 9/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-1598-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Nicotine Promotes Cell Migration Through Alpha7 Nicotinic Acetylcholine Receptor in Gastric Cancer Cells

Abstract

Background

Materials and Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Materials and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 9/2011

Mapping of Genetic Deletions on Chromosome 3 in Colorectal Cancer: Loss of 3p25-pter is Associated with Distant Metastasis and Poor Survival

How Do We Know When a Lymph Node Dissection is Adequate?

Evaluation of 18F-FDG PET/CT and CT/MRI with Histopathologic Correlation in Patients Undergoing Salvage Surgery for Head and Neck Squamous Cell Carcinoma

Papillary Lesions Initially Diagnosed at Ultrasound-guided Vacuum-assisted Breast Biopsy: Rate of Malignancy Based on Subsequent Surgical Excision

A Prospective Study of Total Gastrectomy for CDH1-Positive Hereditary Diffuse Gastric Cancer

Robotics Versus Laparoscopic Radical Hysterectomy with Lymphadenectomy in Patients with Early Cervical Cancer: A Multicenter Study