Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.1.1.6 (CAD)
4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two distinct calcium-sensitive cell-cell adhesion molecules were identified in human epithelial tissues and carcinomas using two monoclonal antibodies raised against vulvar epidermoid carcinoma A-431 and human mammary carcinoma MCF-7 and selected on the basis of their activities to disrupt cell-cell adhesion. In immunoblot analysis, these antibodies, designated NCC-CAD-299 and HECD-1, detected main bands of Mr 118,000 and 124,000, respectively. Purified tryptic fragments of the antigen recognized by NCC-CAD-299 showed cross-reactivity with a rabbit antiserum against mouse P-cadherin, indicating that this molecule was the human homologue of P-cadherin. On the other hand, the antigen recognized by HECD-1 showed essentially the same tissue distribution pattern as E-cadherin in the mouse, suggesting that this molecule is the human homologue of E-cadherin. Availability of these monoclonal antibodies to human P- and E-cadherin allowed us to examine their distributions in human tissues immunohistochemically. Both antigens were detected in epithelial tissues, but they showed distributions that were distinct from each other. The antigen recognized by HECD-1 was expressed in almost all epithelial tissues, while distribution of the other one recognized by NCC-CAD-299 was restricted to the basal or lower layers of stratified epithelia in which both antigens were coexpressed. Moreover, immunohistochemical examination of 44 lung carcinomas showed that both molecules were coexpressed in all of them, and suggested that expression of P-cadherin was closely related to the differentiation of carcinoma cells.
...
PMID:Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. 270 54

The purpose of our study was to determine whether the degree of E- and P-cadherin expression in melanomas correlates with the invasive behavior of the clinical lesions from which the cell lines were derived. Cadherins comprise a family of calcium-dependent cellular adhesion molecules expressed on most cell types that form solid tissues. In the human epidermis, melanocyte cadherin expression may function to maintain the integrity of the epidermal-melanin unit. Employing both immunofluorescence microscopy and fluorescence-activated cell sorter analysis, we localized and quantitated E- and P-cadherin expression on melanoma cell lines derived from primary or metastatic lesions using the monoclonal antibodies HECD-1 and NNC-CAD-299, respectively. Human epidermal melanocytes isolated from neonatal foreskin were evaluated by similar techniques and served as a biologic control. Melanoma cell lines were isolated from primary or metastatic lesions of patients described as having "early," "intermediate," or "advanced disease." Melanoma E- and P-cadherin immunofluorescence, as quantified by fluorescence-activated cell sorter, varied inversely with disease progression. Selected log mean ratios of E-cadherin fluorescence, as compared to human epidermal melanocytes (arbitrarily = 1), ranged from 1.04 in the WM 35 melanoma cell line (low invasive potential) to 0.1 and 0.02 in the WM 983A and 1361A melanoma cell lines (derived from primary lesions with metastases), respectively. Although values for P-cadherin fluorescence were less, the trend of decreasing cadherin amounts with more advanced disease was observed. Melanoma cells appear to express E- and P-cadherin levels inversely related to disease progression. Ultraviolet radiation significantly decreased E- and P-cadherin expression in the human epidermal melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05). Although not statistically significant, E-cadherin expression in the WM 35 melanoma cell line decreased substantially. Thus, ultraviolet radiation may have a direct effect on human epidermal melanocytes and melanoma cell attachment through cadherins within the epidermis or tumor nodules.
...
PMID:Expression of E and P-cadherin by melanoma cells decreases in progressive melanomas and following ultraviolet radiation. 875 77

The invasion-suppressor molecule E-cadherin (E-CAD) can be regulated at multiple levels: synthesis, processing and stability of mRNA; synthesis, processing and stability of protein; localization and posttranslational modification of protein; binding to catenins (E-CAD-associated proteins); and size and charge of cell surface glycosaminoglycans. Loss of E-CAD antigen and of E-CAD function in vivo has been observed with cell lines that homogeneously expressed functional E-CAD in vitro. These observations led to the idea that factors in the host may downmodulate E-CAD on the cancer cells, thereby promoting cell invasion. Nude mouse cancers that were homogeneously E-CAD-positive and noninvasive in vitro, formed by epithelioid MDCK or NMuMG cells, stained heterogeneously for E-CAD; such cancers were invasive and metastatic. The in vivo downmodulation appeared to be transient. Ex vivo cultures from primary cancers, as well as from metastases, produced homogeneously E-CAD-positive and noninvasive cells. Downmodulation did not occur when cells were micro-encapsulated and then implanted in the mouse, suggesting a role for immediate cancer cell-host cell contact. Similar in vitro/in vivo/ex vivo experiments with mouse MO4 fibrosarcoma cells, transfected with E-CAD cDNA under the control of a b-actin promotor, showed downregulation at the transcriptional or mRNA stability level. This downregulation was rapidly reversible upon ex vivo culture of the tumor cells. TGF-bl and IGF-I were found, respectively, to downregulate and upregulate the expression or the function of E-CAD. We speculate that IGF-1 restores the function of E-CAD through interaction of the IGF-I tyrosine kinase receptor with the catenin-actin cytoskeletal complex. In human cancers, immunohistochemistry has revealed changes in E-cadherin that agree with the experimental data on transient downmodulation of the invasion-suppressor function of E-cadherin by host factors.
...
PMID:Downregulation in vivo of the invasion-suppressor molecule E-cadherin in experimental and clinical cancer. 898 64

The effect of cell-to-cell contact on Ca2+ influx and secretory responses in the beta-cell line MIN6 was studied using MIN6 pseudoislets, which are three-dimensional islet-like cell aggregates that develop when MIN6 cells are cultured for 6-8 days on gelatin. The formation of pseudoislets is dependent on the Ca2+-dependent adhesion molecule E-cadherin (E-CAD), since the process can be inhibited by incubation in the absence of Ca2+ or in the presence of an anti-E-CAD antibody. Glucose and alpha-ketoisocaproic acid (KIC) evoked a Ca2+ influx in only a small fraction of the MIN6 monolayer cells, whereas >80% of cell groups within the pseudoislets responded to both nutrients. In contrast, changes in the intracellular free Ca2+ concentration ([Ca2+]i) were observed in all or most monolayer cells or pseudoislet cell groups in response to physical or pharmacological depolarizing stimuli. No significant increase in insulin release was observed from MIN6 monolayer cells in response to nutrient or nonnutrient insulin secretagogues. Conversely, pseudoislets were found to respond significantly to both nutrients and nonnutrients. These results suggest that close cell-to-cell contact improves the functional responsiveness of MIN6 cells and that pseudoislets may therefore serve as a useful research model in the study of beta-cell function.
...
PMID:Pancreatic beta-cell-to-beta-cell interactions are required for integrated responses to nutrient stimuli: enhanced Ca2+ and insulin secretory responses of MIN6 pseudoislets. 1038 45

The function of many transmembrane molecules can be altered by cleavage and subsequent release of their ectodomains. We have investigated ectodomain cleavage of the cell-cell adhesion and signal-transducing molecule E-cadherin. The E-cadherin ectodomain is constitutively shed from the surface of MCF-7 and MDCKts.srcC12 cells in culture. Release of the 80 kDa soluble E-cadherin fragment is stimulated by phorbol-12-myristate-13-acetate and is inhibited by overexpression of the tissue inhibitor of metalloproteinases-2. The metalloproteinases matrilysin and stromelysin-1 both cleave E-cadherin at the cell surface and release sE-CAD into the medium. The soluble E-cadherin fragment thus released inhibits E-cadherin functions in a paracrine way, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation. Our results, therefore, suggest a novel mechanism by which metalloproteinases can influence invasion.
...
PMID:Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. 1111 95

Matrix metalloproteases from the cell surface cleave an 80 kDa E-cadherin fragment (sE-CAD) that induces invasion of cancer cells into collagen type I and inhibits cellular aggregation. Conditioned media from MDCKts.srcCl2 cells at 40 degrees C and 35 degrees C, PCm.src5 and COLO-16 cells at 37 degrees C contained spontaneously released sE-CAD; these 48 h old conditioned media were capable of inhibiting E-cadherin functions in a paracrine way. Here we show direct cleavage of the extracellular domain of E-cadherin by the serine protease plasmin. sE-CAD released by plasmin inhibits E-cadherin functions as evidenced by induction of invasion into collagen type I and inhibition of cellular aggregation. This functional inhibition by sE-CAD was reversed by aprotinin or by immunoadsorption on protein Sepharose 4 fast flow beads with antibodies against the extracellular part of E-cadherin. Our results demonstrate that plasmin produces extracellular E-cadherin fragments which regulate E-cadherin function in cells containing an intact E-cadherin/catenin complex.
...
PMID:Plasmin produces an E-cadherin fragment that stimulates cancer cell invasion. 1192 10

Loss of E-cadherin/catenin mediated cell-cell adhesion and overexpression of matrix metalloproteinases (MMPs) are largely involved in tumor invasion. It has been recently shown that high levels of a soluble 80 kDa fragment of E-cadherin, resulting from a cleavage by MMPs, are found in serum and in urine from cancer patients. Additionally, this soluble E-cadherin (sE-CAD) promotes cell invasion into chick heart and into collagen type I gels. The aim of our study was to examine the mechanism of sE-CAD-induced cell invasion. Since MMPs play a crucial role in invasion, we looked for induction of MMPs by sE-CAD in noninvasive human lung tumor cells 16HBE. An induction of MMP-2, MMP-9 and MT1-MMP expression was observed both at the mRNA and at the protein level in the presence of sE-CAD (in conditioned medium form or in E-cadherin HAV peptide form). No induction of MMP-1, -3 and -7 or variation of the levels of their inhibitors, TIMP-1 and TIMP-2, were detected. The biologic relevance of the sE-CAD-induced MMP upregulation was tested by demonstrating that sE-CAD promotes in vitro cell invasion in a modified Boyden chamber assay. These data provide new insight into mechanisms of tumor invasion by ectodomain shedding of the cell-cell adhesion molecule E-cadherin.
...
PMID:Upregulation of MMPs by soluble E-cadherin in human lung tumor cells. 1276 64

Acute promyelocytic leukaemia (APL) has distinct clinicopathological and molecular features. However, the profile of aberrant gene promoter methylation is undefined. In this study, methylation-specific polymerase chain reaction (MSP) was used to define the methylation status of a panel of nine genes, comprising p15, p16, RARbeta, oestrogen receptor (ER), E-cadherin (E-CAD), p73, caspase 8 (CASP8), VHL and MGMT, in 29 patients with APL. Aberrant methylation of p15, ER, RARbeta, p16 and E-CAD occurred, respectively, in 23 (79%), 14 (48%), six (21%), six (21%) and two (7%) patients at diagnosis, but p73, VHL, CASP8 and MGMT were not methylated in any patients. There was methylation of one gene in 13 patients (45%), two genes in four patients (14%), three genes in six patients (21%) and four genes in three patients (10%). Concurrent methylation of two or more genes occurred in 13 patients (45%). No association was identified between gene methylation and presenting clinicopathological features. However, p15 methylation was significantly associated with an inferior disease-free survival (DFS, P = 0.008), and remained the only poor prognostic factor in multivariate analysis (P = 0.019). In APL, p15, p16, ER and RARbeta were most frequently methylated. This profile is distinct from other types of myeloid leukaemias. p15 methylation has a poor prognostic impact on DFS.
...
PMID:Aberrant gene promoter methylation in acute promyelocytic leukaemia: profile and prognostic significance. 1289 12

Many studies have indicated that the E-cadherin (E-CAD) expression loss is associated with the loss of cellular differentiation and increased cellular invasiveness and can be correlated with poor prognosis in urothelial carcinoma (UC) of the urinary bladder. The aim of this study was to define the role of E-CAD mRNA expression on recurrence, progression and survival in UC of the urinary bladder over a long follow-up period. From 30 patients with bladder UC, enrolled in our previous study, 27 were selected for this study. All patients were re-analyzed in terms of clinical and tumor characteristics, tumor pathological analysis and tumor E-CAD mRNA expression. The data were correlated to 12-year follow-up results. Significant correlations between stage (p=0.002), grade (p=0.008) and E-CAD mRNA expression were reported. E-CAD did not show any correlation in predicting recurrence or progression in bladder UC. The survival analysis demonstrated a significant relationship (p=0.019) between patients with expressed E-CAD mRNA levels and cancer-specific survival. Multivariate analysis demonstrated that expression of E-CAD mRNA levels is an independent prognostic factor in terms of cancer-specific survival in UC of the urinary bladder (p=0.002). Our study is the first to demonstrate that mRNA extraction and Northen blot analysis is to be considered a reliable method to evaluate E-CAD mRNA levels for predicting survival rate in patients affected by urothelial bladder cancers. We stress that a long follow-up period is needed to evaluate the role of molecular factors in predicting prognosis in patients affected by bladder UC.
...
PMID:E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: results from a long-term follow-up study. 1734 38

The aim of this study was to evaluate the relationship between abnormal expression of E-cadherin (E-CAD) and the extracapsular extension of tumors, lymph node involvement and the presence of metastasis in various types of thyroid cancers. Histopathological specimens of 35 benign thyroid lesions and 122 malignant tumors (papillary, follicular, poorly differentiated and undifferentiated cancers) were analyzed. E-CAD immunostaining intensity, its subcellular localization, homogeneity within lesion, and the relation of staining intensity between tumor and surrounding thyroid parenchyma were evaluated. The obtained results show that the variants of differentiated cancers with a poorer prognosis (i.e. tall cell and follicular variants of papillary cancer and widely invasive follicular cancers) present reduced intensity of E-CAD expression, its abnormal localization or heterogeneity of staining more frequently than classical papillary cancers and minimally invasive follicular cancers. However, the assessment of E-CAD expression does not allow the prediction of extrathyroidal growth of thyroid cancers.
...
PMID:E-cadherin expression is more associated with histopathological type of thyroid cancer than with the metastatic potential of tumors. 2326 14


1 2 Next >>

---