Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas

Abstract

We investigated the expression of tight junction proteins in human lung squamous cell carcinomas and adenocarcinomas by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). We found a statistically significant correlation between diagnosis and positivity of tumors with either claudin (CLDN)-1 or CLDN-5. Squamous cell carcinomas and basal cells of bronchial epithelium were positive for CLDN-1 and negative for CLDN-5, whereas adenocarcinomas, normal cylindrical cells and pneumocytes were positive for CLDN-5 and negative for CLDN-1, suggesting different pathways in tumor development and progression. CLDN-4 and ZO-1 staining were detected in both types of tumors, whereas cingulin (CGN) was not detected in squamous cell carcinomas. Quantitative RT-PCR was used to evaluate changes in transcript levels for a large panel of tight junction proteins. In squamous cell carcinomas, we observed statistically significant decreases in the mRNA levels of JAM-1, occludin, CLDN-3, CLDN-4, CLDN-7, CGN, ZO-2 and ZO-3, and an increase in CLDN-1 mRNA. In adenocarcinomas, when transcript levels were compared with bronchial cells, we observed statistically significant decreases in the mRNA levels of CLDN-1, CLDN-3, CLDN-4, CLDN-7, ZO-2 and ZO-3. These results indicate that characterization of tight junction protein expression in human lung tumors can be an additional diagnostic tool and provide new insights on their histogenesis. Modern Pathology (2007) 20, 947-954;

Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells

“…In agreement with our findings, previous data have reported a decrease of ZO-2 in tumor tissues of breast and lung when compared to normal tissue [8,9]. These data are in agreement with the notion that the expression of tight junction proteins is down regulated in carcinomas [21].…”

“…In carcinomas, a reorganization of cell-cell junctions is frequently observed. Accordingly, ZO-2 expression has been shown to be altered in some carcinomas and a downregulation of ZO-2 expression has been reported in lung carcinomas [8,9]. However, in agreement with its ability to shuttle to different cell compartments, other functions, different to its structural role in TJs, have been described for ZO-2 that could contribute to modulate tumor progression.…”

Studies on cell junctions in an ex vivo human lung infection model

“…ZO-1 and occludin were, in line with this study, previously outlined at apical borders of the bronchiolar epithelium in human lung tissue [273,274,279], but non of these studies revealed their appearance as junctional bands. They were rather described as dots or a short line.…”

Epidermal tight junctions in health and disease

“…20 Occludin knockdown experiments reconfirmed its influence on TJ barrier function 24 as well as highlighted its role in differentiation, cell-cell adhesion and keratinocyte susceptibility to apoptosis in response to UVB exposure and TNF-related apoptosis-inducing ligand (TRAIL) stimulation. 20 Reduced expression of occludin was also found in other squamous cell tumors originating in the lung and oral cavity, [114][115][116] thus suggesting it might be a common feature for these types of tumors. Hintsala et al, 113 described an upregulation of cldn-2, 3 and 5 immunostaining in some SCC, but no images were shown to assess if these proteins were expressed in typical sites.…”