title: Impact of smoking on the expression of claudins in lung carcinoma.
abstract: BACKGROUND
  Tight junctions regulate the paracellular permeability and orientation of cells and claudins are key components of tight junctions.
  
  
  OBJECTIVE
  To study the influence of cigarette smoke on claudin expression in vitro and in lung cancer patients.
  
  
  METHODS
  We studied the effect of smoking on claudin expression by exposing a bronchial cell line (BEAS-2B) and two carcinoma cell lines (SK-LU1 and SK-MES1) to tobacco smoke for 48 h and analysed their claudin mRNA expression. The relation between smoked pack years and protein expression of claudins 1-5 and 7 in 344 lung cancer patients was determined by immunohistochemistry.
  
  
  RESULTS
  In BEAS-2B cells and SK-LU1 cells, an initial increase was followed by a decline in the mRNA expression of several claudins. In SK-MES1 cells, no evident elevation in claudin expression was observed. Intense claudin 1 and 4 positivity was found more often in cancer samples of smokers and ex-smokers compared to non-smokers (p<0.001 and p=0.003, respectively). Heavy smokers with longer than 40 pack-years consumption had more often intense claudin 1 (p=0.011), 4 (p=0.050) or 7 (p=0.058) expression in squamous cell carcinoma compared to non-smokers or smokers with fewer pack-years. Claudin 1 positivity predicted a better survival in adenocarcinoma (p=0.044) and in squamous cell carcinoma (p=0.027) and claudin 4 positivity in adenocarcinoma only (p=0.048). In squamous cell carcinoma, claudin 7 positivity was associated with a better survival (p=0.011).
  
  
  CONCLUSIONS
  Bronchial BEAS-2B cells and SK-LU1 cells respond to tobacco smoke by changing their claudin mRNA synthesis and resulting tight junction permeability changes may thus contribute to tobacco induced carcinogenesis both during initiation and progression. This concept is strengthened by findings in the clinical tumour material, where tobacco consumption was associated with claudin expression.
authors.affiliation: Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Aapistie 5A, Oulu, Finland. hmerikal@paju.oulu.fi
authors.forename: Heta
authors.initials: H
authors.lastname: Merikallio
authors.forename: Riitta
authors.initials: R
authors.lastname: Kaarteenaho
authors.forename: Paavo
authors.initials: P
authors.lastname: Pääkkö
authors.forename: Siri
authors.initials: S
authors.lastname: Lehtonen
authors.forename: Pasi
authors.initials: P
authors.lastname: Hirvikoski
authors.forename: Riitta
authors.initials: R
authors.lastname: Mäkitaro
authors.forename: Terttu
authors.initials: T
authors.lastname: Harju
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000368:Aged; D001980:Bronchi / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality; D002460:Cell Line; D045744:Cell Line, Tumor; D057167:Claudins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000378:metabolism* / Q000401:mortality; D019108:Tight Junctions
chemical_list: D057167:Claudins