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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from 40 patients with newly diagnosed bladder cancer (28 superficial tumours (pTa and pT1) and 12 muscle-invasive tumours) were assessed by enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble E-cadherin (sE-cadherin), soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Corresponding frozen sections of primary tumour were analysed for E-cadherin expression using the monoclonal antibody, HECD-1 and standard immunohistochemistry. Patients with bladder cancer had significantly higher concentrations of sE-cadherin compared with a control group (P = 0.017). No difference was found between the two groups with regard to sE-selection (P = 0.403), sVCAM-1 (P = 0.942) and sICAM-1 (P = 0.092). High levels of sE-cadherin were related to poor histological grade (P = 0.009), number of superficial tumours at presentation (P = 0.008) and a positive 3 month check cytoscopy in superficial disease (P = 0.036). Abnormal E-cadherin expression was associated with increasing tumour stage (P = 0.009) and grade (P = 0.03). There was no correlation between high levels of soluble E-cadherin in sera and abnormal E-cadherin expression by the tumour (P = 0.077). Elevated levels of sE-cadherin are found in sera of patients with bladder cancer and correlate with known prognostic factors.
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PMID:Cell adhesion molecules in bladder cancer: soluble serum E-cadherin correlates with predictors of recurrence. 876 73

Loss of E-cadherin-mediated adhesion is an important step in the progression of many carcinomas. In model systems, it has been shown that cadherin function requires not only proper E-cadherin expression but also its linkage to the cytoskeleton through catenins. Hence, defects in catenins may cause defective E-cadherin function, and catenins as well as E-cadherin might constitute prognostic indicators. Here, we extend our previous study on E-cadherin in bladder cancer (Cancer Res., 53: 3241-3245, 1993). We have evaluated the expression of E-cadherin-associated cytoplasmic molecules (alpha-, beta-, and gamma-catenins and p120cas) to clarify whether or not the pattern of their expression could provide additional prognostic information beyond that from E-cadherin alone. Forty-eight frozen bladder tumor specimens and 9 samples of normal urothelium were studied by immunohistochemistry. A discrepancy between the E-cadherin and catenin expression pattern was seen in 20.8% of cases. Abnormal expression of each molecule is significantly correlated with tumor grade (P < 0.01) and stage (P < 0.01). Reduced expression of all of the molecules correlates with poor survival (P < 0.01 for each variable). Proportional hazard regression analysis showed that beta-catenin, E-cadherin, and alpha-catenin have strong predictive value, whereas plakoglobin and p120cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, alpha-catenin, or beta-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, beta-catenin, E-cadherin, and alpha-catenin have similar prognostic values. Therefore, from a practical point of view, the expression of any of these proteins can be of prognostic value for patients with bladder cancer.
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PMID:Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors. 879 85

Alterations in the E-cadherin-mediated cell-cell adhesion pathway are commonly observed in urologic malignancies. This issue has been addressed most thoroughly in prostate cancer. Whereas both cadherin and catenin dysfunction have been seen in human prostate cancers, only down-regulation of E-cadherin has been shown for bladder cancer and renal-cell carcinoma. Although studies in bladder cancer and renal-cell carcinoma are less mature than studies in prostate cancer, they support the hypothesis that immunostaining for E-cadherin may be of significance for both diagnostic and prognostic purposes. Finally, the E-cadherin-mediated cell-cell adhesion pathway may represent a novel chemotherapeutic target for bladder cancer, prostate cancer, and renal-cell carcinoma. Obviously, more work lies ahead to translate these important observations from the bench to the bedside.
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PMID:The E-cadherin cell-cell adhesion pathway in urologic malignancies. 911 56

Aberrant Wnt gene expression is involved in the development of breast cancer, but its role in other tumours is unknown. Wnts regulate cadherin function, previously shown to be more commonly deregulated in invasive bladder cancer. This study investigated whether factors upstream of cadherins were aberrantly expressed in superficial bladder cancer. The expression of one transforming (Wnt7b) and one non-transforming (Wnt5a) Wnt gene in four human bladder carcinoma cell lines, and in normal human bladder tissues (n = 8) and bladder cancers (n = 48) were analysed by ribonuclease protection analysis. All cell lines expressed an approximately equal level of Wnt7b mRNA. Wnt5a and Wnt7b mRNAs were both expressed in normal bladder tissues and bladder tumours. The median expression of Wnt7b was fourfold higher in superficial tumours (n = 29) than in normal tissues (n = 8, P = 0.002) and five fold higher than in invasive tumours (n = 17, P = 0.003). There was no significant difference between normal tissues and invasive tumours (P = 0.3). The expression of Wnt5a did not vary significantly between normal tissues and superficial tumours (P = 0.4), normal tissues and invasive tumours (P = 0.3) or superficial tumours and invasive tumours (P = 0.2). The differential expression of Wnt7b suggests a role in the early events of superficial bladder tumorigenesis involving cell adhesion and provides further evidence of different pathways of evolution of superficial and invasive cancer.
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PMID:High expression of Wnt7b in human superficial bladder cancer vs invasive bladder cancer. 946 Oct 4

E-cadherin, the epithelium-specific cadherin, is known to play a major role in tumor progression in many human carcinomas, via intercellular homophilic Ca2+-dependent adhesion. This adhesion is mediated by a group of cytoplasmic proteins, including the alpha-, beta- and gamma-catenins that link the E-cadherin to the actin cytoskeleton. Recent studies have shown that loss or reduction of either E-cadherin or catenin expression was strictly related to clinicopathological data in bladder tumors, and E-cadherin might constitute prognostic factors in bladder carcinogenesis. Here we continued a preliminary work on E-cadherin in bladder cancer. In an effort to evaluate their possible prognostic value, we investigated both E-cadherin and catenins in 99 bladder tumors by immunohistochemistry. E-cadherin and all the catenins were strongly expressed in normal urothelium. Regarding histopathological data, the tumors examined showed that the disrupted expression of each molecule, except for gamma-catenin, was directly related to increasing tumor grade (mainly for alpha- and beta-catenin) and deep invasion (p < or = 0.01). The aberrant expression of E-cadherin and beta-catenin was also correlated to the presence of distant metastasis (p < 0.05). However, only abnormal expression of a-catenin was associated with poor survival (p = 0.037). Therefore our results suggest that alpha-catenin is directly involved in tumor invasion and dedifferentiation and is the only protein of any prognostic value, albeit low in patients with bladder cancer.
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PMID:Expression of E-cadherin and alpha-,beta- and gamma-catenins in human bladder carcinomas: are they good prognostic factors? 970 39

Three bladder cell lines (EJ138, RT112/84 and T24/83) were used to examine the expression of E-cadherin, desmoglein, their associated proteins and their role in cell-cell dissociation and invasion using hepatocyte growth factor/scatter factor (HGF/SF). Both immunocytochemistry and Western blotting revealed that RT112/84 cells expressed high levels of E-cadherin, alpha-, beta-, and gamma-catenins. However, there was no expression of E-cadherin and very low levels of alpha- and beta-catenin expression detected in both EJ138 and T24/83 cells. In contrast, all three cell lines were found to express desmoglein, desmoplakin and c-Met. An in vitro invasion assay showed that both EJ138 and T24/83 cells were highly invasive, however, RT112/84 cells were found to have very limited invasion. Invasion of RT112/84 cells was significantly increased by inclusion of either antibody to E-cadherin or motogen (HGF/SF) in the culture medium. This did not appear to be the case for EJ138 and T24/83 cells. Using immunoprecipitation, HGF/SF induced tyrosine phosphorylation of beta-catenin but not desmoplakin. It is concluded that E-cadherin plays a stronger role than desmosomal cadherin in the control of the in vitro invasion of bladder cancer cells. Activation of beta-catenin and subsequent dysfunction of E-cadherin may be a key mechanism in the induction of invasion by the motogen, HGF/SF.
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PMID:Cell-cell adhesion molecules and their associated proteins in bladder cancer cells and their role in mitogen induced cell-cell dissociation and invasion. 1022 96

Reduced expression of the adhesion molecule E-cadherin has been associated with increased invasiveness and poorer survival in patients with bladder cancer. We have examined soluble E-cadherin (sE-cadherin) and total protein concentrations in urine from patients with bladder cancer (n = 34), non-neoplastic benign urological diseases (n = 14) and healthy controls (n = 21) to determine their diagnostic and prognostic significance. Soluble E-cadherin concentrations of the cancer group were significantly higher (P < 0.001) than those of the controls but the benign group was not significantly different from either the cancer group or the controls. When sE-cadherin concentrations were adjusted for creatinine, similar but more statistically significant results were obtained and the benign group was significantly elevated compared with the controls (P < 0.01). No differences were apparent between the invasive (pT1-4) and non-invasive (pTa) cancers. Urinary total protein concentrations in the cancer group were significantly higher than the controls (P < 0.001) and the benign group (P < 0.05) although no difference was seen between the benign group and patients with non-invasive (pTa) cancer or between the benign group and controls. When expressed as the protein/creatinine index, results were similar but more statistically significant and a significant difference was seen between invasive and non-invasive cancers (P < 0.01). Only the protein/creatinine index correlated significantly with stage of the tumour (P < 0.01). It is concluded that urinary sE-cadherin measurements are of no greater value than urinary total protein.
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PMID:Urinary concentrations of the soluble adhesion molecule E-cadherin and total protein in patients with bladder cancer. 1039 8

Loss or reduced expression of E-cadherin has been shown to be associated with poor survival in patients with bladder cancer. In numerous cases, loss of E-cadherin expression in bladder tumors has been accompanied by continued association of catenins with the membrane, suggestive of the expression of an alternative cadherin member. In this study we examined 75 bladder tumors using immunohistochemistry for the expression of E-, P-cadherin, and alpha-, beta-, and gamma-catenins. As reported previously, loss or reduced E-cadherin expression is a frequent event in late stage bladder cancer, accompanied by less frequent alterations associated with different catenin family members. Analysis of 51 tumors for expression of E-, P-, and N-cadherin showed P-cadherin localized to the basal cell layers of normal urothelium, with retention of expression in the majority of tumors. In low-grade tumors P-cadherin was found localized to an expanded basal cell compartment, contrasting with the more extensive staining observed in late stage tumors. Membranous P-cadherin staining was often found in the absence of E-cadherin staining. N-cadherin is not expressed in normal bladder mucosa, but detection of this cadherin member was recorded in 39% (20/51) of bladder tumors. Unlike P-cadherin, membranous N-cadherin was detected in focal regions within tumors, representing novel expression in urothelial neoplastic progression. Although focal N-cadherin staining was observed in 3 noninvasive lesions, the majority of tumors expressing N-cadherin were invasive (17/20). Coexpression of E-, P-, and N-cadherin was recorded in 5 grade 2 bladder tumors. Expression of P-cadherin is maintained throughout bladder tumorigenesis, accompanied by aberrant expression of N-cadherin. Clearly, neither P- nor N-cadherin act in an invasive-suppressor mode in bladder cancer, but whether they have a primary role to play in urothelial neoplastic progression has yet to be established.
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PMID:Expression of classic cadherins type I in urothelial neoplastic progression. 1117 90

Decreased expression of the epithelial cell adhesion protein E-Cadherin occurs in several forms of human epithelial-derived cancers, including bladder cancers. We investigated the possibility that aberrant methylation of the CpG island flanking the 5' transcriptional start site of the e-cadherin gene is responsible for the decreased expression of this gene in bladder cancer, similar to the relationship previously seen between e-cadherin methylation and gene expression in other types of human cancers. Using methylation-specific polymerase chain reaction, we found methylation of this CpG island in 20 of 47 cases (43%) of bladder neoplasms ranging from low-grade papillary neoplasms to advanced, invasive cancers. When methylation status was compared to immunochemical staining for E-Cadherin, we found significantly diminished levels of E-Cadherin expression in 14 of 15 cases (93%) with methylation of the gene. We also found decreased expression of E-Cadherin, although to a somewhat lesser extent, in a high percentage (77%) of the cases without methylation of the gene. Although these data suggest a relationship between e-cadherin CpG island methylation and decreased gene expression, it evident that other mechanisms also contribute to decreased expression of this gene in bladder neoplasia. Remarkably, we also found low levels of e-cadherin methylation in urothelial cells from three of nine (33%) histologically normal bladders, with all three of the normal bladder samples with methylated e-cadherin being from individuals older than 70 years of age. Thus, methylation of the e-cadherin CpG island may occur normally in this tissue with aging as well as in low-grade papillary neoplasms, and is not specific to cancer in the bladder. This finding of methylation in normal urothelial cells from elderly individuals is provocative with respect to a possible link between aging and increased risk for bladder cancer, but it suggests limitations on the usefulness of using methylation of e-cadherin as a molecular marker for detection of bladder cancer.
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PMID:Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals. 1154 75

Classical cadherins such as E- and P-cadherin are transmembrane proteins that mediate specific cell-to-cell adhesion and are important to tissue development and function. Cadherin function can be modulated by various means, including proteolytic cleavage of the extracellular adhesion domain from the cells' surface, yielding large soluble fragments termed (soluble) sE- or sP-cadherin. In people with certain carcinomas, sE-cadherin can be detected at elevated levels in the serum and sometimes can serve as a prognostic marker. Soluble E-cadherin also is found in urine of patients with bladder cancer. In addition to being present in bodily fluids of cancer patients, sE- and sP-cadherin are present in the serum of healthy people, suggesting that shedding of cadherins is a normal event. Here, we report high levels of 80 kDa sP-cadherin in human milk. In the lactating mammary gland tissue, P-cadherin appears to be a protein secreted by epithelial cells, rather than an adhesion protein. This is in contrast to the non-lactating mammary gland where P-cadherin is restricted to myoepithelial cells, and is present at sites of cell-cell contact.
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PMID:Soluble fragment of P-cadherin adhesion protein found in human milk. 1221 Jul 48


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