title: Role of nicotinic acetylcholine receptors in cell proliferation and tumour invasion in broncho-pulmonary carcinomas.
abstract: OBJECTIVE
  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.
  
  
  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
  α5, α7, β2 and β4 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, α5, β2 and β4 subunits were essentially identified in tumour cells at invasive fronts, whereas α7 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 α7 nAChR. Both α7 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, α7 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.
  
  
  CONCLUSIONS
  α7 nAChR and heteromeric α5*β2*β4* 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 α7 nAChR antagonists to prevent lung cancer progression should be restricted to poorly differentiated tumours.
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France.
authors.forename: Kahina
authors.initials: K
authors.lastname: Medjber
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France.
authors.forename: Mohamed Lamine
authors.initials: ML
authors.lastname: Freidja
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Grelet
authors.affiliation: Laboratory of Histology, CHU of Reims, 51092 Reims, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Lorenzato
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Maouche
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nawrocki-Raby
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France; Laboratory of Histology, CHU of Reims, 51092 Reims, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France; Laboratory of Histology, CHU of Reims, 51092 Reims, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims-Champagne-Ardenne, 51100 Reims, France. Electronic address: jm.tournier@univ-reims.fr.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Tournier
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic
keywords: Invasion; Nicotinic receptor; Non-small cell lung cancer; Proliferation