• Korean Journal of Clinical Laboratory Science
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• v.55 no.1
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• pp.37-44
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• 2023

Enterotoxigenic Bacteroides fragilis (ETBF) has been reported to promote colitis and colon cancer through the secretion of B. fragilis toxin (BFT), a zinc-dependent metalloprotease. In colonic epithelial cells, BFT induces the cleavage of E-cadherin into the 80 kDa ectodomain and the 33 kDa membrane-bound intracellular domain. The resulting membrane-tethered fragment is then cleaved by γ-secretase forming the 28 kDa E-cadherin intracellular fragment. The 28 kDa cytoplasmic fragment is then degraded by an unknown mechanism. In this study, we found that the 28 kDa E-cadherin intracellular fragment was degraded by the proteasome complex. In addition, we found that this sequential E-cadherin cleavage mechanism is found not only in colonic epithelial cells but also in the human breast cancer cell line, BT-474. Finally, we report that staurosporine also induces E-cadherin cleavage in the human breast cancer cell line, MCF7, through γ-secretase. However, further degradation of the 28 kDa E-cadherin intracellular domain is not dependent on the proteasome complex. These results suggest that the BFT-induced E-cadherin cleavage mechanism is conserved in both colonic and breast cancer cells. This observation indicates that ETBF may also play a role in the carcinogenesis of tissues other than the colon.

• Journal of Life Science
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• v.19 no.6
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• pp.705-710
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• 2009

Sodium butyrate (NaBt), a naturally occurring short chain fatty acid derived from carbohydrate metabolism in the gut, is known to exhibit strong anti-cancer potentials in various human cancer cells; however, its action mechanism is poorly understood. In the present study, we demonstrated that NaBt up-regulates levels of E-cadherin, a key cell adhesion molecule implicated as a tumor suppressor, in a cell type-specific manner. Although levels of p21, a potential activator for E-cadherin expression, were also up-regulated by treatment with NaBt in several types of cells, it does not seem to be associated with the activation of E-cadherin in the NaBt-treated cells. Instead, the data from promoter analysis suggest that NaBt up-regulates expression of E-cadherin at the transcription level by enhancing its promoter strength via a CCAAT-box. The elevated E-cadherin in the presence of NaBt was primarily localized at the cell-cell contacts, converting Hep3B cells into a more differentiated form.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5149-5153
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• 2012

Introduction: This study assessed the relationship of E-cadherin mRNA and protein expression with the diagnosis of lung cancer with the aim of providing an auxiliary diagnostic method. Methods: Semi-quantitative nested RT-PCR and western blotting were applied to detect E-cadherin mRNA transcripts and protein, respectively, in 30 cases of diagnostic lung cancer, 30 cases of clinically suspected patients with lung cancer and 30 cases of other disease. Immunohistochemical staining was also used to detect E-cadherin. Results: Remarkably decreased levels of relative E-cadherin mRNA value and increased E-cadherin protein negativity were observed in probable lung cancer, when compared with possible lung cancer and others. With a threshold of 1.45, relative E-cadherin mRNA value showed a sensitivity of 90% and a specifity of 83% for the diagnosis of lung cancer. The combination of decreased relative E-cadherin mRNA value and negative E-cadherin protein increased the specificity and sensitivity. Conclusion: These data suggest that Chinese patients with diagnostic lung cancer have similar decreased levels of relative E-cadherin mRNA and E-cadherin protein value in the lung cancer tissues as in lung cancer patients in other countries. Measurement of relative E-cadherin mRNA and protein values in lung cancer tissues has potential for lung cancer diagnosis.

• The Korean Journal of Cytopathology
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• v.12 no.2
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• pp.81-87
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• 2001

The differentiation between reactive mesothelial and carcinoma cells in serous effusion cytology can be a diagnostic challenge based on morphology alone. The expression of some cell adhesion molecules may be helpful in the differential diagnosis. This study evaluated the usefulness of E-cadherin Immunocytochemistry for discrimination of carcinoma cells from reactive mesothelial cells. Alcohol fixed, paraffin embedded cell blocks taken from 42 reactive and 102 malignant serous effusions with histologically confirmed diagnoses were immunostained with monoclonal antibody to E-cadherin by LSAB method. E-cadherin expression was identified in only 2 benign reactive serous effusions(5%) whereas 91 malignant serous effusions(89%) expressed E-cadherin The differences in immunostaining for E-cadherin between reactive and malignant serous effusions were statistically significant(p < 0.001). The sensitivity and specificity of the E-cadherin immunostaining for carcinoma cells were 89% and 95%, respectively. In conclusion, E-cadherin is a useful diagnostic adjunct for differentiation between reactive mesothelial and carcinoma cells in serous effusions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2003-2007
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• 2012

Purpose: E-cadherin is a transmemberane protein which is responsible for adhesion of endothelial cells. The aim of our study was to assess existing evidence of associations between reduced expression of E-cadherin and prognosis of ovarian cancer with a discussion of potential approaches to exploiting any prognostic value for improved clinical management. Methods: We conducted a meta-analysis of 9 studies (n=915 patients) focusing on the correlation of reduced expression of E-cadherin with overall survival. Data were synthesized with random or fixed effect hazard ratios. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for E-cadherin positivity, and methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that reduced expression of E-cadherin positivity was associated with poor overall survival (OS), HR= 2.10, 95% CI:1.13-3.06. Conclusion: The overall survival of the E-cadherin negative group with ovarian cancer was significant poorer than the E-cadherin positive group. Upregulation of E-cadherin is an attractive therapeutic approach that could exert significant effects on clinical outcome of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5715-5719
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• 2012

The relation between cyclooxygenase enzymes and E-cadherin, along with the roles of these markers in the prediction of survival in optimally cytoreduced serous ovarian cancer patients was investigated. Individuals who underwent primary staging surgery and achieved optimal cytoreduction (largest residual tumor volume <1 cm) constituted the study population. Specimens of 32 cases were immunohistochemically examined for cyclooxygenase-1, cyclooxygenase-2, and E-cadherin. Two could not be evaluated for E-cadherin and cyclooxygenase-1. Overall, 14/30, 19/30, and 15/32 cases were positive for E-cadherin, cyclooxygenase-1, and cyclooxygenase-2, respectively. The expressions of E-cadherin and cyclooxygenase-2 were inversely correlated (p:0.02). E-cadherin expression was related with favorable survival (p<0.001). The relation between the expression of cyclooxygenase enzymes and poor survival did not reach statistical significance. On multivariate analysis, E-cadherin appeared as an independent prognostic factor for survival. In conclusion, E-cadherin expression is strongly linked with favorable survival. E-cadherin and cyclooxygenase 2 may interact with each other during the carcinogenesis-invasion process. Further studies clarifying the relation between E-cadherin and cyclooxygenase enzymes may lead to new preventive and therapeutic targets in ovarian cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.177-182
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• 2009

Purpose: Colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. E-cadherin plays a key role in the establishment and maintenance of epithelial tissue structure and cell-cell adhesion. The purpose of this study is to evaluate E-cadherin expression in colonic epithelium of various colitis in children. Methods: The expressions of E-cadherin were examined in 39 cases of colonic mucosal biopsy specimen using immunohistochemical staining. When more than 50 percent of cells exhibited uniformly the same intensity and pattern of immunostaining as the adjacent normal mucosa, the antigen expression was considered normal. Abnormal expression was defined when less than 50 percent of cells stained, when cells showed a heterogeneously weak or altered distribution, or when complete absence of staining was observed. Results: Fifteen cases with non-specific colitis (38.5%), 7 cases of with Crohn's disease (17.9%), 5 cases of infectious colitis and milk protein sensitive proctocolitis (12.8%), 3 cases of ulcerative colitis (7.7%), 2 cases of Henoch-Schonlein purpura colitis (5.1%), one case of Behcet's disease and ischemic colitis (2.6%) were included in this study. E-cadherin expression was decreased in all kinds of colitis. Reduced expression of E-cadherin was observed in 77 percent of cases. E-cadherin was weaker or no expression in reparative epithelium and "ulcer associated cell lineage". Conclusion: Altered expression of E-cadherin occurs during mucosal inflammation in any kinds of colitis. These changes may be involved in promoting cell migration during epithelial restitution of the gastrointestinal mucosa.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1557-1561
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• 2012

Objective: To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer (NSCLC) and its association with clinical pathological parameters, and to explore the relationship between downregulation of E-cadherin gene expression and the methylation status of its promoter region. Methods: Nested methylation-specific PCR was performed to examine CpG methylation within the 5' CpG island of the E-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lung cancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Results: Of thirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the 12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayed reduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA was unavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene. Conclusion: These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of NSCLC.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.156-163
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• 2004

Purpose: While E-cadherin in normal cells induces calciumdependent cell-cell adhesion, in malignant cell, it plays a role in invasion and metastasis with a reduction of adhesion. Serum soluble E-cadherin is a result of the reduction of the cellular E-cadherin molecule and is found in the circulation of normal individuals, but it is particularly known to be increased in patients with malignancies. Accordingly, through checking the level of serum soluble E-cadherin in patients with gastric cancer and analyzing it in the view of clinicopathology, we investigated whether serum soluble E-cadherin could be translated into a clinicopathologic esult and used as a tumor marker. Materials and Methods: The investigation targeted 88 patients who had been diagnosed as having gastric cancer by the Department of Surgery, St. Mary's Hospital, from October 1, 2002, to July 30, 2003, and who had under gone performed surgery. We measured the level of preoperative serum E-cadherin in the 88 patients by unsing ELISA. Among them, we collected gastric cancer tissues from 54 patients and executed immunohistochemistry for E-cadherin. The samples were compared with normal tissues in terms of both serum E-cadherin level and immunohistochemistry level, as well as with other clinicopathologic factors. Result: The mean serum E-cadherin level of the 88 patients was 4368.7 ng/ml and was significantly higher than the level in 12 normal control patients, 3335.5 ng/ml (P=0.016). In terms of clinicopathology, the serum level of E-cadherin was significantly correlated with increasing age (P=0.0006) and was higher in positive venous invasion patients (P=0.0005). When the E-cadherin immunohistochemical stain was compared with the serum E-cadherin level in 54 patients, no significant statistically meaningful result was obtained (P=0.2881). However, 4 patients with serum E-cadherin levels about 6000 ng/ml were classified into the lower expression group ($<80\%$ of E-cadherin immunohistochemicals stain. In the analysis for 36 patients who were early gastric cancer patients, the serum E-cadherin level in lymph-node-metastatic patients was higher than it was in the other patients (P=0.0442). Conclusion: The serum E-cadherin level in gastric cancer patients was higher than the level in normal control patients. In advanced gastric cancer patients, that the difference was increased. Also, since the E-cadherin level correlated with the serum E-cadherin level with venous invasion, it can be used as an effective tumor marker for gastric cancer. Particularly, in that the serum E-cadherin level correlated with lymph node metastasis in early gastic cancer, it can be used when a therapeutic method for early gastric cancer is selected.