Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E- and N-cadherins are proteins involved in intercellular adhesion and are localized, e.g., in the adherens junctions of epithelial cells. Kidney tubules express these molecules in a distinctive pattern, the expression of N-cadherin being restricted to proximal tubules and that of E-cadherin to distal tubules and collecting ducts. Renal cell carcinomas (RCCs) and oncocytomas are considered to originate from these tubular epithelia. To find out whether cadherins could serve as markers for a cellular origin of these tumors, we studied the expression of E- and N-cadherins in RCCs and oncocytomas, in cell lines derived from RCCs as well as in tumors grown in nude mice. Most RCCs co-expressed E- and N-cadherins, as did 2 of the 4 cell lines studied. The expression pattern did not correlate with the histological grade of the tumors, and even the least differentiated tumors, as well as metastases, showed expression of cadherins. Renal oncocytomas expressed E-cadherin but not N-cadherin, which is in line with previous studies that have proposed a collecting duct origin for these tumors. Papillary renal neoplasms, a separate entity usually not classified as RCC, expressed neither of the cadherins studied despite the abundant expression of beta-catenin. Our results suggest that most RCCs co-express the characteristic adhesion molecules of both proximal and distal tubules, which makes it questionable whether the origin of these tumors can be reliably located to any distinct part of the renal tubule. Our results also suggest that in RCCs the increased histological grade is not directly associated with changes in the expression of either of the cadherins, indicating other mechanisms underlying the deficient capacity to form polarized tubular structures.
 ...
PMID:Expression of E- and N-cadherin in renal cell carcinomas, in renal cell carcinoma cell lines in vitro and in their xenografts. 855 Feb 43

The HaCa4 cell line, derived from a mouse skin carcinoma induced by Harvey murine sarcoma virus, is highly tumorigenic when injected into nude mice and produces multiple metastases in the lungs. HaCa4 cells express high levels of viral Ha-ras oncogene products, anomalously synthesize the embryonic/simple epithelial keratin K8, and have lost the expression of the cell-cell adhesion receptor E-cadherin (E-CD). E-CD(+) cell clones (E62 and E24), obtained by transfection of an exogenous E-CD cDNA into HaCa4 cells, had a decreased ability to migrate through type IV collagen matrices. However, the E-CD (+) E62 clone remained as metastatic as the parental cell line, whereas the E24 clone, which does not take up the exogenous cDNA but spontaneously switches on the endogenous E-CD gene, suppressed the metastatic phenotype although it maintained its tumorigenicity. E24 cells had fivefold to sixfold lower levels of viral Ha-ras mRNA and p21 protein than the other cell lines. In addition, they did not synthesize K8 but rather switched on keratin K19. The comparison of E-CD proteins synthesized by E62 and E24 cell lines revealed no structural or functional differences because both localized at cell-cell contacts and associated with alpha-catenin, beta-catenin, and plakoglobin. Furthermore, E-CD was still expressed in metastatic lung nodules produced by E62 cells. These results suggest that suppression of the metastatic phenotype in E24 cells occurs independently of E-CD expression and correlates with decreased levels of the oncogenic ras p21 protein.
 ...
PMID:Suppression of the metastatic phenotype of a mouse skin carcinoma cell line independent of E-cadherin expression and correlated with reduced Ha-ras oncogene products. 859 77

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process.
 ...
PMID:Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. 916 40

Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.
 ...
PMID:Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). 925 Jan 46

The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E-cadherin and alpha- and beta-catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico-pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E-cadherin, alpha-catenin, and beta-catenin was found in 74, 60, and 72 per cent, respectively. Expression of E-cadherin and alpha-catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta-catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E-cadherin and beta-catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E-cadherin, alpha-catenin and beta-catenin are related events. Furthermore, expression of at least E-cadherin and beta-catenin is significantly correlated with poor prognosis.
 ...
PMID:Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. 934 37

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.
Invasion Metastasis 1997
PMID:Expression of E-cadherin and alpha-,beta- and gamma-catenins in human bladder carcinomas: are they good prognostic factors? 970 39

It has recently been shown that tumor-associated antigens (TAAs) can evoke tumor-specific T-cell-defined immune responses in cancer patients, thereby offering the possibility of treating patients with such antigens. To develop T-cell-based immunotherapeutic approaches for renal cell carcinoma (RCC), we studied the mRNA expression profile of the TAAs RAGE-1, tyrosinase, MAGE-1, MAGE-2, NY-ESO-1, Melan-A/MART-1, glycoprotein (gp) 75, gp100, beta-catenin, PRAME, and MUM-1 in 14 human RCC cell lines and in tissue specimens of 37 primary RCCs, 2 related metastases, and 33 specimens of normal renal epithelium. Reverse transcription-PCR was performed with TAA-reactive primers, and the specificity of the PCR products was confirmed by Southern blot and/or direct sequencing. PRAME (10 of 14 cell lines), RAGE-1 (7 of 14 cell lines), and gp75 (4 of 14 cell lines) antigens were expressed in a high percentage of RCC cell lines, although the level of TAA expression varied among the different RCC cell lines. However, low levels of TAA expression in RCC cells are sufficient for recognition by TAA-specific CTLs. Transcription of tyrosinase, Melan-A/MART-1, MAGE-1, MAGE-2, NY-ESO-1, gp100, beta-catenin, and MUM-1 was not detected in any RCC cell line. Approximately 50% of surgically removed neoplasias expressed at least one TAA. RAGE-1 mRNA expression was found in 8 of 39 (21%) RCC samples, PRAME mRNA expression was found in 15 of 39 (40%) RCC samples, and gp75 mRNA expression was found in 4 of 39 (11%) RCC samples, but the expression levels of these TAAs were heterogeneous in the different RCC lesions. One RCC specimen expressed MAGE-2, whereas transcription was not detected in any RCC specimen for MAGE-1, NY-ESO-1, tyrosinase, Melan-A/MART-1, gp100, beta-catenin, and MUM-1. The normal kidney epithelium samples were negative for any TAA tested. Thus, RAGE-1, PRAME, and gp75 expression is found with a different frequency in surgically removed lesions and in RCC cell lines, suggesting that a subgroup of RCC patients could be selected for immunotherapeutic strategies that may benefit from immunization against the RAGE-1, gp75, and/or PRAME antigens. However, additional targets for T-cell-based immunotherapy of RCC have yet to be identified.
 ...
PMID:Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? 975 17

In the metastatic process, various cell-cell adhesion molecules seem to play an important role. E-cadherin, a transmembrane protein with an extracellular and an intracellular domain, is one of the key players involved in cell-cell adhesion. The function of E-cadherin in preventing metastasis in tumour development is believed to be dependent on intracellular catenins. In a previous study, the expression of E-cadherin was examined in a series of human breast carcinomas. In that study, down-regulation of E-cadherin failed to correlate with lymph node and/or distant metastasis. In the present study, the expression of alpha-, beta-, and gamma-catenins has been examined in a subset of the same tumours in order to evaluate their possible role in breast cancer metastasis. Tumour tissues from 90 primary breast carcinomas were immunostained for alpha-, beta-, and gamma-catenins. Reduced or absent immunoreactivity in the tumour tissue was seen in 63 (70.0 per cent) for alpha-catenin, in 50 (55.6 per cent) for beta-catenin, and in 50 (55.6 per cent) for gamma-catenin. Reduced expression of each of the catenins alone failed to correlate to metastasis. However, when all of the four proteins (E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin) were analysed as one group, a significant association was seen between reduction in immunoreactivity of at least one of these four proteins and the presence of metastases. These results indicate that if one of these proteins is down-regulated, the function of the others in suppressing metastasis is altered. A significant association was seen between lobular invasive tumours and beta-catenin expression.
 ...
PMID:E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. 977 79

Nasopharyngeal carcinoma (NPC) is predominantly of the undifferentiated histological subtype. Histological differentiation is of limited prognostic significance in NPC. Recent studies have suggested that downregulation of the cadherin-catenin cell adhesion complex may play a crucial role in the initial stage of cancer invasion and metastasis and is associated with poor prognosis in human cancers. Expression of E-cadherin has not been reported previously in NPC, and its prognostic value in NPC is unknown. The purpose of this study was to examine the expression pattern of E-cadherin and its associated partner, beta-catenin, in NPC and their possible applications as prognostic markers to predict the clinical outcome of NPC. Expression of the E-cadherin and beta-catenin was examined by immunohistochemical methods in 74 cases of primary NPC and 17 of their corresponding lymph node metastases. Normal nasopharyngeal epithelium showed strong and homogeneous immunocytochemical staining of E-cadherin and beta-catenin at the cell membranes and intercellular junctions. In contrast, primary NPC showed variable and heterogeneous staining patterns of E-cadherin and beta-catenin. Loss of membranous E-cadherin expression was significantly associated with advanced stages of diseases (P<.001). Eighty percent to ninety percent of NPC in stages IV and V (Ho's staging), respectively, showed a reduced (<35%) membranous staining of E-cadherin compared with normal nasopharyngeal epithelium. Expression of beta-catenin also was downregulated in advanced NPC. Ninety percent to one hundred percent of NPC in stages IV and V (Ho's staging) expressed a reduction (<35%) of imnmunocytochemical staining of beta-catenin. The expression pattern of beta-catenin staining was strongly associated with the expression of E-cadherin (P<.001). Unlike E-cadherin, nuclear staining of beta-catenin expression was observed in some of the primary NPC and lymph node metastasis. Reduced expression of E-cadherin and beta-catenin expression was associated with a shorter survival of NPC patients (P<.001). In advanced NPC patients (stages IV and V), a significant difference in survival was observed in tumors with higher or lower levels of E-cadherin expression (P=.0224, log-rank test). These observations suggests that expression of E-cadherin and beta-catenin may have prognostic values in NPC patients.
 ...
PMID:Downregulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. 1020 69

The interaction of the adenomatous polyposis coli (APC) tumor-suppressor protein and the intracellular cell-adhesion protein beta-catenin is crucial for the development of colorectal tumors. Since functional nuclear complexes of beta-catenin with transcription factors have been identified recently, the knowledge of level and distribution of beta-catenin in sporadic colorectal tumors will give important insights into the intracellular mechanism of sporadic colorectal tumor initiation and progression. In contrast to the familiar adenomatous polyposis syndrome and to the majority of sporadic colorectal tumors, Peutz-Jeghers (PJ) syndrome is not caused by mutations in the APC gene. Since PJ syndrome is an inherited disease with an increased risk for gastrointestinal adenocarcinoma, whether beta-catenin plays a similarly important role for the development of PJ polyps should be further investigated. For these reasons we analyzed the distribution of beta-catenin in a total of 60 sporadic colorectal tumors at different stages of progression and in 6 PJ polyps. In addition to the localization at the cell-to-cell border membranes, fluorescence immunohistochemistry revealed a nuclear accumulation of beta-catenin in single tumor cells of 10/14 small adenomas with mild dysplasia and in 14/16 adenomas with moderate dysplasia. Further tumor progression is accompanied by an expansion of cells with increased level of nuclear and cytoplasmic beta-catenin. These cells were observed in 5/16 adenomas with moderate dysplasia and in 15/15 adenomas with severe dysplasia. In all adenocarcinomas investigated, as well as in the corresponding lymph node metastases, a sub-population of tumor cells exhibited a remarkably increased level of beta-catenin within the entire cytoplasm and the nucleus. In contrast to the situation in sporadic colorectal tumors, nuclear and cytoplasmic beta-catenin was not increased in PJ polyps. These results point to an extensive redistribution of beta-catenin, which starts early in colorectal tumorigenesis. The nuclear accumulation in single cells of small adenomas can be considered as the first visible sign of the loss of APC function. Thus the immunohistochemical detection of beta-catenin distribution could serve as a criterion for estimating the malignant potential in the clinico-pathological evaluation of colon tumors during their early progression.
 ...
PMID:Intracellular distribution of beta-catenin in colorectal adenomas, carcinomas and Peutz-Jeghers polyps. 1035 35


1 2 3 4 5 6 7 8 9 10 Next >>