9076

CLDN1

claudin 1;CLDN1;claudin 1

claudin-1|senescence-associated epithelial membrane protein 1

3q28-q29

protein-coding

INTRODUCTION: We compared levels of protein and mRNA expression of three members of the claudin (CLDN) family in malignant breast tumours and benign lesions. METHODS: Altogether, 56 sections from 52 surgically resected breast specimens were analyzed for CLDN1, CLDN3 and CLDN4 expression by immunohistochemistry. mRNA was also analyzed using real-time PCR in 17 of the 52 cases. RESULTS: CLDNs were rarely observed exclusively at tight junction structures. CLDN1 was present in the membrane of normal duct cells and in some of the cell membranes from ductal carcinoma in situ, and was frequently observed in eight out of nine areas of apocrine metaplasia, whereas invasive tumours were negative for CLDN1 or it was present in a scattered distribution among such tumour cells (in 36/39 malignant tumours). CLDN3 was present in 49 of the 56 sections and CLDN4 was present in all 56 tissue sections. However, CLDN4 was highly positive in normal epithelial cells and was decreased or absent in 17 out of 21 ductal carcinoma grade 1, in special types of breast carcinoma (mucinous, papillary, tubular) and in areas of apocrine metaplasia. CLDN1 mRNA was downregulated by 12-fold in the sample (tumour) group as compared with the control group using GAPDH as the reference gene. CLDN3 and CLDN4 mRNA exhibited no difference in expression between invasive tumours and surrounding tissue. CONCLUSIONS: The significant loss of CLDN1 protein in breast cancer cells suggests that CLDN1 may play a role in invasion and metastasis. The loss of CLDN4 expression in areas of apocrine metaplasia and in the majority of grade 1 invasive carcinomas also suggests a particular role for this protein in mammary glandular cell differentiation and carcinogenesis.

In this study, we analyzed Claudin-1 and Claudin-4 expressions in colon carcinomas. We investigated the relationship between the expression of these tight junction proteins and clinicopathologic parameters. Claudin-1 and 4 expressions were determined by immunohistochemical methods, and the rate of cells expressing these tight junction proteins were calculated with stereologic methods. Fifty-nine colon cancer cases were enrolled in the study group. Claudin-1 and 4 expressions were found to be significantly lower in cases with lymph node metastasis. Mean staining rates of Claudin-1 and 4 in lymph node (+) cases were 36.1+/-20.1 and 58+/-28.9, while in lymph node (-) cases, these were 63.8+/-25.9 and 72.3+/-25.6, respectively (p=0.0005 for Claudin-1, p=0.049 for Claudin-4). The mean staining rate for Claudin-1 in adenomatous polyps was significantly higher than incarcinomas (77.13+/-23.4 and 50.6+/-26.93, respectively) (p=0.003), while it was quite similar for Claudin-4 (65.4+/-26.9 and 65.3+/-27.9, respectively). In this study, we demonstrated Claudin-1 and 4 expressions in colon cancer cases. Claudin-1 expression seems to be more prominent in adenomatous polyps as compared with cancer cases. expression of Claudin-1 decreases significantly in the presence of lymph node metastasis and diminishes in mucinous carcinoma cases, indicating a negative correlation between Claudin-1 expression and neoplastic progression.

BACKGROUND: The molecular and morphological alterations of the tight junctions in hepatic metastatic lesions are poorly understood. The possible involvement of claudin-1 (CL-1), which is one of the major tight junctional proteins, was investigated in the tumorigenesis of hepatic metastasis in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 14 patients with hepatic metastasis of CRC who underwent surgical treatment from January 2007 until December 2010 at the Kurume University Hospital in Fukuoka, were examined. CRC tissue specimens were analyzed to determine whether the levels of CL-1 correlated with clinicopathological factors and to determine the roles of CL-1, beta-catenin, and E-cadherin in the alterations of the tight junctions during tumorigenesis. RESULTS: In seven cases, the tumors were located in the colon, while the other seven tumors were found in the rectum. There were eight cases of synchronous liver metastasis, while there were six cases of metachronous liver metastasis. The levels of the CL-1 protein were up-regulated in CRC and in hepatic metastatic lesions. The levels of beta-catenin were positive or up-regulated in the primary CRC lesions and in hepatic metastatic lesions. Despite the finding that the levels of E-cadherin were decreased in CRC, they were clearly up-regulated in hepatic metastatic lesions in this study. CONCLUSION: This study demonstrated that CL-1 levels were up-regulated in liver metastatic lesions from primary CRC lesions. Moreover, the levels of E-cadherin were increased in liver metastatic lesions, which may point to the existence of interactions between CL-1 and E-cadherin in hepatic metastatic lesions. These observations suggest that CL-1 plays a pivotal role in the regulation of cellular morphology and in the behavior of metastatic processes in CRC.

OBJECTIVE: Colonic carcinoma is one of the most common cancers worldwide. Recently, the possible involvement of claudin-1, one of the major tight junction proteins, in the process of tumorigenesis has been suggested. Also, claudin-1 has emerged as a potential prognostic factor in different types of tumors. The aim of this study was to detect caludin-1 expression in colonic carcinoma and to correlate its expression with clinicopathological variables in an attempt to delineate its role as a potential new prognostic marker. MATERIAL AND METHODS: Immunohistochemical expression of claudin-1 was assessed in 50 Egyptian patients with colonic adenocarcinoma. The predictive performance of claudin-1 expression was statistically evaluated. RESULTS: Decreased claudin-1 expression was found in 62% of colonic adenocarcinoma cases while similar expression was found in 38% of the cases. Statistical analysis showed a statistically significant inverse correlation between claudin-1 expression and tumor grade, depth of invasion, lymph node involvement, and tumor stage. Regression analysis showed that claudin-1 decreased expression significantly predicts that the tumor is of a high grade, high stage, and is associated with lymph node involvement. ROC curve analysis showed that claudin-1 had a sensitivity of 88.24% and a specificity of 81.25% for the prediction of tumor stage and a sensitivity of 73.33% and a specificity of 82.86% for the prediction of lymph node involvement. CONCLUSIONS: Claudin-1 decreased expression in colonic carcinoma contributes to tumor dedifferentiation, invasion and metastasis. Claudin-1 expression could be used as a predictor of colonic carcinoma stage and lymph node status with a high sensitivity and specificity.

The aim of this study was to evaluate the immunoexpression of claudin-1 and Nm23-H1 in metastatic and nonmetastatic lower lip squamous-cell carcinoma (LLSCC). Twenty LLSCCs with regional nodal metastasis and 20 LLSCCs without metastases were selected. The percentage of claudin-1 staining and the staining intensity and percentage of Nm23-H1 staining in each tumor core were assessed. metastatic tumors exhibited higher expression of claudin-1 than nonmetastatic tumors (P = 0.030). Similarly, stage III and IV LLSCCs showed higher expression of claudin-1 than stages I and II (P = 0.026). The percentage of claudin-1 staining was scored as 2 in most well-differentiated and moderately differentiated tumors, whereas poorly differentiated tumors showed a relatively similar distribution of scores 2, 1, and 0 (P = 0.648). Regarding Nm23-H1, there was a predominance of negative cases for both metastatic and nonmetastatic tumors (P = 0.235). In addition, no significant differences in the percentage of Nm23-H1-negative and Nm23-H1-positive cases were observed regarding the clinical staging (P = 0.430) and the histologic grading of malignancy (P = 0.702). The results of this study suggest an important role of claudin-1 in the development of metastasis in LLSCCs. In contrast, the present findings do not support a significant role of Nm23-H1 in metastasis suppression of LLSCC.

RATIONALE: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. OBJECTIVES: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. METHODS: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. MEASUREMENTS AND MAIN RESULTS: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-alpha], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. CONCLUSIONS: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

CONCLUSIONS: Altered expression of claudin-1, claudin-7, and tricellulin in early tonsillar squamous cell carcinoma (SCC) independent of human papilloma virus (HPV) infection may lead to tumor progression. OBJECTIVES: Integral tight junction proteins, the claudins and tricellulin, play a crucial role in all tissues. HPV is significantly associated with tonsillar SCC. We sought to determine the expression of claudin-1, claudin-7, and tricellulin in HPV-infected and HPV-free tonsillar SCC. METHODS: Twenty-eight tonsillar SCCs were studied by immunohistochemical analysis and real-time reverse transcription polymerase chain reaction with in situ hybridization analysis. RESULTS: Compared with normal tissues, claudin-1 was strongly expressed, whereas claudin-7 and tricellulin were weakly expressed or were absent in primary SCC and metastatic lymph nodes. Claudin-7 and tricellulin were markedly reduced at all stages of tumor development. In situ hybridization analysis showed no correlation between HPV infection and altered expression of the tight junction proteins.