Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreased expression of the cell-cell adhesion molecule, E-cadherin, promotes dedifferentiation and invasiveness of human carcinoma cells, whereas this process can be reversed by reexpression of E-cadherin (U. H. Frixen et al., J. Cell Biol., 113: 173-185, 1991; J. H. Schipper et al., Cancer Res., 51: 6328-6337, 1991). In this work we studied the involvement of extracellular matrix-degrading proteases in E-cadherin-dependent tumor cell invasion. When T47D and MCF-7 human differentiated breast carcinoma cells were treated with the E-cadherin antibody DECMA (decompacting monoclonal antibody) the cells dissociated from each other and lost their epithelioid morphology, paralleled with a rise in the secretion of urokinase-type plasminogen activator (uPA) into the extracellular milieu as determined by zymography. The stimulation of uPA required protein and RNA synthesis. Furthermore, when DECMA-treated T47D cells were cultured on artificial collagen matrices the induced invasiveness correlated with accumulation of uPA in the culture medium, and uPA antibodies inhibited this invasion process. Actin filaments which are thought to be associated with the cytoplasmic part of E-cadherin were disrupted after treatment of T47D cells with DECMA. These results suggest a link between cell-cell adhesion, the integrity of actin filaments, and the regulation of uPA biosynthesis.
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PMID:Stimulation of urokinase-type plasminogen activator expression by blockage of E-cadherin-dependent cell-cell adhesion. 833 68

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.
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PMID:Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro. 834 83

Two members of the cadherin family of intercellular adhesion molecules are found in normal breast tissue: E-(epithelial) cadherin is present in both luminal and myoepithelial cells, whereas P- (placental) cadherin is confined to myoepithelium. There is experimental evidence that loss of E-cadherin is associated with increased invasiveness of malignant cells in vitro, which stimulated us to examine the presence and distribution of E- and P-cadherin in breast carcinomas by means of immunohistochemical staining. E-Cadherin was present in all in situ and invasive ductal carcinomas examined, although it had a patchy distribution and the staining was of variable intensity. However, in 83 per cent of invasive lobular carcinomas and all lobular carcinomas in situ there was complete loss of E-cadherin expression. In the remaining 17 per cent of invasive lobular tumours, E-cadherin appeared to have an abnormal distribution within the cytoplasm with variable expression on the cell membrane. P-Cadherin, by contrast, was absent from all benign breast luminal epithelium and 25 carcinomas of ductal and lobular type. It was found in only one carcinoma of lobular type. We suggest that loss of cell-cell adhesion mediated by E-cadherin plays a part in the characteristic morphology of lobular carcinomas.
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PMID:Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. 838 97

The cell-cell adhesion molecule E-cadherin has been shown to suppress invasive growth of epithelial cells in vitro, and loss of its expression is thought to be important in invasion and metastatic potential of epithelial tumors in vivo. We retrospectively studied the level of E-cadherin expression in 50 primary head and neck squamous-cell carcinomas (HNSCC) by immunohistochemical methods, on frozen sections, using anti-E-cadherin monoclonal antibody (MAb) 6F9. It concerned patients with different stages of carcinoma of larynx or oral cavity who had been treated with curative intention 30 months or more before. Percentages of membranous stained tumor cells were scored in 1 of 5 categories. Scores were generally low, as in 11/50 lesions < or = 5% cells were stained, and in 19/50 lesions only 6-25% cells showed membranous staining. In 9 lymph-node metastases evaluated, E-cadherin expression was in the same range as in the primary tumors. There was a significant correlation between the level of membranous E-cadherin expression in the primary tumor and the degree of differentiation. No relation was found with tumor size (pT) or regional lymph-node classification (pN). Nevertheless, 29 patients surviving > or = 30 months without evidence of disease had significantly higher levels of membranous E-cadherin expression in their primary tumors than 10 patients with unfavorable clinical course clearly related to recurrent and/or metastatic HNSCC. Moreover, this could only partially be explained by distinctions in differentiation grade between both groups. Our results suggest that membranous E-cadherin expression has prognostic importance in patients with HNSCC.
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PMID:E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. 840 85

Expression of the epithelial cell adhesion molecule E-cadherin in primary and metastatic gastric carcinoma was examined using immunohistochemical analyses. Compared to normal mucosa, 92% of the primary tumors (n = 60) showed reduced E-cadherin expression, suggesting that down-regulation of this cell adhesion molecule is a common early event in gastric tumorigenesis. No significant correlation was found between E-cadherin expression and tumor diameter, lymphatic vessel invasion, Borrmann classification, lymph node status, or manifest metastases. Although advanced tumors (tumor stage 3/4) showed a loss of E-cadherin-positive cells (< or = 50% cells/lesion, P = 0.0168), the most significant correlation was observed between low E-cadherin expression and cellular dedifferentiation (grading 3/4, P = 0.0001) and disintegration of tissue architecture (Lauren and WHO classifications, P = 0.0001). Low E-cadherin expression (< or = 50% cells/lesion) was associated with tumor recurrence (P = 0.0013) and mortality (P = 0.0246). E-cadherin expression in metastatic lesions (n = 58) also correlated with the degree of glandular differentiation (P = 0.0001). Significant correlation (rs = 0.686) was observed between E-cadherin expression in primary and metastatic lesions from individual patients (n = 39). However, while metastases derived from E-cadherin-negative tumors remained negative, those originating from E-cadherin-positive tumors frequently demonstrated increased levels of expression. Evaluation of multiple metastases in 11 patients revealed uniformly strong E-cadherin expression in liver metastases, suggesting a possible regulatory role of the microenvironment.
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PMID:E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. 845 43

Immunohistochemical investigations were carried out on the localization and expression of the Ca(2+)-dependent intercellular adhesion molecule E-cadherin in human gingiva and gingival carcinoma. Although E-cadherin did not appear in the parakeratinized layer of either clinically healthy or inflamed gingiva, it did appear strongly in the prickle layer and somewhat more weakly in the basal layer. Immunogold particles reactive to anti-E-cadherin monoclonal antibody in the electron microscopic findings were localized only in the vicinity of the desmosomes of the prickle and basal layers. In the case of gingival carcinoma, although E-cadherin was strongly expressed in the cells surrounding the keratinized region in the cancer nests, the expression decreased towards the marginal portion of the cancer nests. The distribution of E-cadherin in these cells may be dependent on the condition of the cancer cells that are potentially invasive. These findings suggest that cells of the parakeratinized layer of gingiva and cells of the marginal portion of the gingival carcinoma nests may easily detach or invade. In addition, the findings suggest that the gingival carcinoma used in this study tended to be invasive.
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PMID:Localization of E-cadherin adhesion molecules in human gingiva and gingival carcinoma. 848 37

It has been suggested that the selective loss of E-cadherin expression can generate invasiveness in human carcinoma cells and might be a predictor of metastasis. Frozen sections of samples from 44 patients, 43 with suspected large bowel cancer and one with a liver recurrence were examined for E-cadherin expression using the antibody 6F9 specific for the human E-cadherin molecule. Twelve of the 40 patients with carcinoma already had lymph node involvement at the time of surgery. Samples from the primary carcinomas of only nine of these 12 patients showed reduced E-cadherin expression. However, the one lymph node with metastatic spread examined did show reduced E-cadherin expression. Four of the 40 carcinoma patients had liver involvement at the time of surgery. The primary carcinoma samples from only three of these four patients showed reduced E-cadherin expression. In addition only two out of the three liver metastases examined showed reduced expression. The primary carcinoma samples from seven patients with no evidence of tumour spread also exhibited reduced expression. Overall, analysis of the data suggests that there is no absolute correlation between reduced E-cadherin expression and tumour spread in carcinomas of the large bowel.
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PMID:The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis. 849 23

We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(q13), del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. beta 1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.
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PMID:Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice. 852 16

Metastasis of colon carcinomas is assumed to be caused by multiple steps, which include a loss of cell adhesion that results in the release of carcinoma cells from the original tumor tissue. A human colon carcinoma cell line COKFu was established from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion and without expression of E-cadherin mRNA and protein. This cell line was co-transfected with mouse E-cadherin cDNA in an expression vector and a neomycin-resistant gene. The parental carcinoma cells had a spindle shape and were scattered, whereas the transfected cells, which expressed exogenous E-cadherin gene, showed a more compact shape with strong cell-cell adhesion and with increased adhesiveness to collagen gel. These cells showed a significantly low anchorage independency (2-7%) and decreased invasiveness (30%) compared to the parental cells. Growth rate of transfectants was decreased both in vitro and in the subcutis of nude mice, with decreased lymphnode metastasis in the case of intravenous injection. It was additionally found that activity of 62 kd gelatinase, secreted from parental cells, was lost or decreased in E-cadherin-transfected cells. These results suggest that E-cadherin is not only involved in the cell-cell adhesion of colon carcinomas, it also has a wider effect, including cell-substratum adhesion and the regulation of proteinase secretion from the cells, resulting in partial suppression of invasiveness and tumorigenic growth.
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PMID:Increased cell-substratum adhesion, and decreased gelatinase secretion and cell growth, induced by E-cadherin transfection of human colon carcinoma cells. 854 11

Cell-cell adhesion in tissue is mainly regulated by homotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including alpha- and beta-catenin. Although we previously demonstrated that alpha-catenin is crucial for cadherin function in vivo, little is known about the role of beta-catenin. We examined the expression of beta-catenin in human carcinoma samples along with normal tissue (esophagus, stomach, and colon) by immunostaining using our antibody for beta-catenin. Normal epithelium strongly expressed beta-catenin. However, beta-catenin expression was frequently reduced in primary tumors of the esophagus (10 of 15, 67%), stomach (9 of 19, 47%), and colon (11 of 22, 50%). From an immunoprecipitation study, we found that beta-catenin forms a complex with E-cadherin not only in the normal epithelium but also in cancerous tissues. In coexpression patterns of E-cadherin and beta-catenin, 43 (77%) of the 56 tumors showed a similar expression of both molecules, whereas the other 13 tumors (23%) showed positive staining for E-cadherin and reduced expression of beta-catenin. These findings suggest that beta-catenin forms a complex with E-cadherin in vivo and down-regulation of beta-catenin expression is associated with malignant transformation.
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PMID:Beta-catenin expression in human cancers. 854 24


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