Role of nicotinic acetylcholine receptors in cell proliferation and tumour invasion in broncho-pulmonary carcinomas.
Fiche publication
Date publication
mars 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr POLETTE Myriam, Dr TOURNIER Jean-Marie
Tous les auteurs :
Medjber K, Freidja ML, Grelet S, Lorenzato M, Maouche K, Nawrocki-Raby B, Birembaut P, Polette M, Tournier JM
Lien Pubmed
Résumé
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: alpha5, alpha7, beta2 and beta4 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, alpha5, beta2 and beta4 subunits were essentially identified in tumour cells at invasive fronts, whereas alpha7 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 alpha7 nAChR. Both alpha7 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, alpha7 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: alpha7 nAChR and heteromeric alpha5*beta2*beta4* 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 alpha7 nAChR antagonists to prevent lung cancer progression should be restricted to poorly differentiated tumours.
Référence
Lung Cancer. 2015 Mar;87(3):258-64