Role of nicotinic acetylcholine receptors in cell proliferation and tumour invasion in broncho-pulmonary carcinomas
Role of nicotinic acetylcholine receptors in cell proliferation and tumour invasion in broncho-pulmonary carcinomas
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DOI：
10.1016/j.lungcan.2015.01.001
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发表时间：
2015-03-01
期刊：
影响因子：
5.3
通讯作者：
Tournier, Jean-Marie
中科院分区：
文献类型：
--
作者：
Medjber, Kahina;Freidja, Mohamed Lamine;Tournier, Jean-Marie
Objectives: Nicotine and its associated nicotinic acetylcholine receptors (nAChRs) are believed to be involved in the progression of lung carcinomas. This study aimed at examining the localization of nAChRs in human lung tumours and, by using primary cultures of tumour cells derived from these tumours, determining the nAChR roles in cell proliferation and tumour invasion.Materials and methods: Immunohistochemistry was used to assess nAChR expression in non-small cell lung carcinomas (NSCLC). Primary cultures of tumour cells were established from NSCLC tissue samples and the effects of nicotine and nAChR antagonists on cell proliferation and invasion were assessed.Results: alpha 5, alpha 7, beta 2 and beta 4 nAChR subunits were expressed in all adenocarcinomas (AC) and squamous cell carcinomas (SCC) tissue samples. In AC, all subunits were identified in glandular structures. In SCC, alpha 5, beta 2 and beta 4 subunits were essentially identified in tumour cells at invasive fronts, whereas alpha 7 subunit was mainly present in the most differentiated tumour cells and less frequently at invasive fronts. In AC and SCC, there was an inverse distribution of cell proliferation marker Ki-67 and alpha 7 nAChR. Both alpha 7 nAChR and heteromeric nAChRs positively regulated in vitro tumour invasion in NSCLC. Heteromeric nAChRs had a limited activity in regulating tumour cell proliferation in vitro. In contrast, alpha 7 nAChR was a repressor of proliferation in tumour cells isolated from well differentiated NSCLC but mediated the pro-proliferative activity of nicotine in cells isolated from poorly differentiated NSCLC.Conclusion: alpha 7 nAChR and heteromeric alpha 5*beta 2*beta 4* nAChRs play a role in ex vivo tumour progression by stimulating invasion and, depending on the differentiation status of the tumour, by regulating proliferation. Our results suggest that the use of alpha 7 nAChR antagonists to prevent lung cancer progression should be restricted to poorly differentiated tumours. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
