Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Aapistie 5A, Oulu, Finland.
Eur J Cancer. 2011 Mar;47(4):620-30. doi: 10.1016/j.ejca.2010.10.017. Epub 2010 Nov 22.
Tight junctions regulate the paracellular permeability and orientation of cells and claudins are key components of tight junctions.
To study the influence of cigarette smoke on claudin expression in vitro and in lung cancer patients.
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.
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).
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.
紧密连接调节细胞旁通透性和细胞定向，而克劳丁是紧密连接的关键组成部分。
研究体外吸烟和肺癌患者中克劳丁表达的影响。
我们通过暴露支气管细胞系（BEAS-2B）和两种癌细胞系（SK-LU1 和 SK-MES1）于烟草烟雾中 48 小时来研究吸烟对克劳丁表达的影响，并分析它们的克劳丁 mRNA 表达。通过免疫组织化学法确定 344 例肺癌患者吸烟包年数与克劳丁 1-5 和 7 蛋白表达之间的关系。
在 BEAS-2B 细胞和 SK-LU1 细胞中，几种克劳丁的 mRNA 表达最初增加，随后下降。在 SK-MES1 细胞中，克劳丁表达没有明显升高。与不吸烟者相比，吸烟者和前吸烟者的癌症样本中克劳丁 1 和 4 的阳性表达更为强烈（分别为 p<0.001 和 p=0.003）。与不吸烟者或吸烟包年数较少的吸烟者相比，吸烟时间超过 40 年的重度吸烟者的鳞状细胞癌中克劳丁 1（p=0.011）、4（p=0.050）或 7（p=0.058）表达更为强烈。克劳丁 1 阳性预测腺癌（p=0.044）和鳞状细胞癌（p=0.027）的生存更好，而仅在腺癌中克劳丁 4 阳性预测生存更好（p=0.048）。在鳞状细胞癌中，克劳丁 7 阳性与生存更好相关（p=0.011）。
支气管 BEAS-2B 细胞和 SK-LU1 细胞通过改变克劳丁 mRNA 合成对烟草烟雾作出反应，由此导致的紧密连接通透性变化可能有助于烟草诱导的癌变的发生和进展。这一概念在临床肿瘤标本中得到了加强，在该标本中，吸烟与克劳丁表达有关。
