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

Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. They are divided into subclasses. The E- and P-cadherins are regarded as the epithelial subtype. Their expression has been demonstrated in many different carcinoma types. Using immunomorphological techniques, we studied the expression of E-cadherin in a series of 145 human brain tumours with the monoclonal antibody 5H9. Western blot analysis was used to confirm the immunohistochemical data. The tumour types represented were astrocytoma WHO I (n = 7), astrocytoma WHO II (n = 6), astrocytoma WHO III (n = 14), glioblastoma WHO IV (n = 8), oligodendroglioma WHO II (n = 5), ependymoma WHO II (n = 5), choroid plexus papilloma WHO I (n = 5), pineoblastoma WHO IV (n = 5), medulloblastoma WHO IV (n = 5), neurinoma WHO I (n = 5), meningioma WHO I and WHO III (n = 75) and pituitary adenoma WHO I (n = 5). Only choroid plexus papillomas (5/5) and meningiomas showed E-cadherin expression. In benign meningiomas (n = 45; 100%), positive E-cadherin immunoreactivity was found regardless of the histomorphological subtype. E-Cadherin was also expressed in 21 WHO I meningiomas (100%) invading dura, bone, brain, and muscle. In contrast, E-cadherin was absent from the majority of morphologically malignant meningiomas (6/9, 66.6%). In addition, in recurrent meningiomas (n = 9), E-cadherin expression in the recurrent tumours was identical to that in the primary neoplasm except in cases with malignant progression, where the malignant recurrent tumour was E-cadherin negative. In 2 cases of metastasizing meningiomas, no E-cadherin immunoreactivity was found in the primary tumours or their metastases.
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PMID:E-Cadherin in human brain tumours: loss of immunoreactivity in malignant meningiomas. 950 62

The acquisition of a metastatic phenotype by epithelial cells implicates a series of changes altering their differentiation, their overall behavior and morphology. In the present study, we have examined the relationships between the cellular morphology, E-cadherin expression, matrix metalloproteinases expression and in vitro invasive properties in two human bronchial immortalized cell lines. The (16HBE14o-) cell line which did not show any invasive abilities in the Boyden chamber assay displayed a typical epithelial morphology in monolayer, expressed high levels of E-cadherin and synthesized neither MMP-2 and MT1-MMP nor vimentin. In contrast, the BZR cell line which was highly invasive displayed a more elongated phenotype in monolayer, did not produce E-cadherin but expressed vimentin, MMP-2 and MT1-MMP. Our data therefore suggest that the metastatic progression of broncho-pulmonary cancer cells results in a cellular dedifferentiation and the gain of some mesenchymal attributes (loss of E-cadherin and expression of vimentin) associated with enhanced degradative properties (expression of metalloproteinases).
Clin Exp Metastasis 1998 Feb
PMID:Association of fibroblastoid features with the invasive phenotype in human bronchial cancer cell lines. 951 91

As a model system for the identification of genes involved in the progression of human breast cancer, differential gene expression in cell lines MCF-7 and MCF-7ADR was investigated. The latter cell line is derived from the former. Cell line MCF-7 is estrogen receptor-positive, vimentin-negative and uninvasive in the Matrigel outgrowth assay and in the nude mouse, while MCF-7ADR is estrogen receptor-negative, hormone-resistant, vimentin-positive, invasive in the Matrigel outgrowth assay and in the nude mouse and resistant to adriamycin due to overexpression of glycoprotein gp170. We have shown that tumor progression in this model system is mediated by transcriptional regulation of mitochondria-related genes, proteases, transmembrane receptors and cell cycle-related gene proteins. Among the genes differentially regulated at the transcriptional level in the cell lines MCF-7 and MCF-7ADR are a new mitochondrial transcript, mitochondrial creatine kinase, matrix metalloproteinase-1, stromelysin-3, urokinase and its receptor, tissue factor, E-cadherin, epidermal growth factor receptor, transmembrane proteins Mat-8 and progression associated protein (PAP), cyclin E, cyclin-dependent kinase-2 and cell cycle inhibitory proteins p16, p21 and p27.
Clin Exp Metastasis 1998 Feb
PMID:Molecular analysis of two mammary carcinoma cell lines at the transcriptional level as a model system for progression of breast cancer. 951 94

We have analysed the role of hepatocyte growth factor/scatter factor (HGF/SF) in the process of morphogenesis and metastasis of epithelial (carcinoma) cells. HGF/SF induces various morphogenic responses in epithelial cells that derive from different tissues when these are grown in three-dimensional gels, e.g. branching tubules in kidney, breast, and prostate epithelial cells, crypt-like structures with brush border in colon epithelial cells, and alveolar-like aggregates in lung and pancreas cells. Epithelial cells are thus able to form complex structures in vitro which resemble the structures formed in the organ they originate from. We also examined the response of human breast carcinoma cells to HGF/SF in vivo. MDA MB 435 cells transfected with HGF/SF were injected into the mammary fat pad of nude mice, where they form tumours which spontaneously metastasize to the lungs. We found that expression of HGF/SF promoted metastasis whereas expression of the cell adhesion molecule E-cadherin was inhibitory. Moreover, expression of E-cadherin reconstituted the ability of the cells to form complex structures in response to HGF/SF in vitro. These data demonstrate that the different responses to HGF/SF depend on the state of the epithelial cells: morphogenesis requires epithelial differentiation and cell polarity, whereas metastasis is observed when the cells have lost their epithelial characteristics. Moreover, we have recently identified Gab-1 as a direct-binding substrate of the c-Met receptor. Gab-1 binds to c-Met phosphorylated on tyrosine residues, but not to a number of other tyrosine kinases from different subfamilies. A newly identified proline-rich domain of Gab-1 is responsible for the binding to the bidentate docking site in c-Met. Expression of Gab-1 in epithelial cells is sufficient to induce c-Met-specific cellular responses which include the formation of branching tubules. Thus, Gab-1 seem to correspond to the substrate of the c-Met receptor tyrosine kinase that mediates the epithelial morphogenesis.
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PMID:Role of HGF/SF and c-Met in morphogenesis and metastasis of epithelial cells. 952 74

ELAM is an E-Selectin adhesion molecule involved in the inflammatory process but it is also thought to potentially participate in the development of blood borne metastases, by facilitating tumour cell adhesion to vessels wall. ELAM expression in tumours was immunohistochemically investigated in 203 breast carcinomas. Frozen tissue sections were probed with monoclonal anti ELAM (Clone 1.2B6) using automated and quantitative immunoperoxidase systems. A positive anti-ELAM immunoreaction was observed in 113 tumours (57%). The mean surface of positive tumours varied from 3% to 50% (mean = 11.75%, SD = 8.7) and was correlated with histoprognostic indicators and tumour expression of various antigens detected according to the same method as ELAM. The results showed that ELAM immunoexpression was independent of the tumour size, grade and type and of the nodal status but significantly increased parallel to patients' age (p<0. 01). ELAM expression was independent of Ki-67/MIB1, anti-P53 and anti-Bcl2, anti-CD44v, anti-c-erbB-2, anti-CD31, anti-RE/RP, anti-PS2, and anti-VLA3 immunoreactions. But ELAM expression correlated with that of the VCAM vascular cell adhesion molecule (p=0.0004), VLA2 (p<0.0001), P-glycoprotein (p=0.025), and of Cathepsin D to a lower degree (p=0.06) and inversely correlated with E-cadherin (p=0.03). The results suggest that endothelial cell activation is independent of tumour cell proliferative activity and of stromal angiogenesis and that the precise role and regulation of ELAM in tumours remains to be elucidated. Also the clinical relevance of ELAM immunohistochemical expression requires further investigation and correlation with patients' follow-up.
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PMID:ELAM selectin expression in breast carcinomas detected by automated and quantitative immunohistochemical assays. 953 26

The aim of this study was to compare the immunophenotype of the human colon cancer cell line HT29 tumour deposits in the lung which occurred spontaneously after subcutaneous implantation with those which arose after intravenous injection into severe combined immunodeficient (scid) mice. Irrespective of the route of implantation the colon cancer cells were readily observed in the lungs of the scid mice. Similar patterns of immunoreactivity for the proliferative markers (MiB-1, PCNA), and for the tumour suppressor gene (p53) were detected in both groups, and for carcinoembryonic antigen, with only minor quantitative differences in levels of marker expression. Whereas the marker CD44 variant 6 gave very little reaction after either route, cytokeratin expression varied amongst the different cytokeratins (CK 7, 18 or 20), and with the route of implantation. CA125 and E-cadherin were weakly expressed after intravenous injection, but generally not after subcutaneous implantation. Vimentin was not demonstrated in any of the specimens examined. In general, the expression of proliferative markers, and of oncogenes, appears to be independent of the implantation route, whilst expression of cell adhesion molecules can be dependent on the route of implantation.
Invasion Metastasis 1997
PMID:Immunophenotype of human HT29 colon cancer cell metastases in the lungs of scid mice: spontaneous versus artificial metastases. 956 Oct 26

E-cadherin is a calcium-dependent, epithelial cell adhesion molecule whose reduced expression has been associated with tumor dedifferentiation and increased lymph node metastasis in clinical studies involving several carcinomas. In this study, 111 patients who had previously undergone complete resection and systematic mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) were studied retrospectively. In the primary tumor, as well as in the lymph node metastases, E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1; Takara, Otsu, Japan). There was a significant inverse correlation between E-cadherin expression and lymph node stage (Pearson correlation coefficient -0.52, p = 0.0001) as well as tumor differentiation (Pearson correlation coefficient -0.27, p = 0.005). Moreover, Kaplan and Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival in log rank testing (p = 0.006). In the patient group with the highest proportion of E-cadherin positive tumor cells, 60% of the patients were still estimated to be alive at 36 mo, versus 32% of the patients in the group classified as showing negative E-cadherin expression. Our findings provide clinical evidence that reduced E-cadherin expression is associated with tumor dedifferentiation, increased lymphogenous metastasis and poor survival. It seems therefore that E-cadherin expression might be an important prognostic factor in NSCLC.
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PMID:Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer. 956 56

Reduction or loss of the intercellular junctions known as desmosomes may contribute to the invasive and metastatic behaviour of various carcinomas. Previous studies have shown that metastasis of oral squamous cell carcinomas of the head and neck correlates with a reduction in immunohistochemical staining for desmoplakin and desmoglein at the invasion front. The primary aim of the present study was to extend these observations to include a third component of desmosomes, the glycoprotein desmocollin. An additional aim was to determine whether the differentiation status of tumours is reflected in their staining for cytokeratins 1, 13, and 19, and, if so, whether these parameters correlate with desmosomal staining and/or metastasis. The study included 54 primary tumours of which 28 showed lymph node metastases. The results of this investigation show that tumours can be divided into three groups according to whether they have lost staining for no, one or more than one desmosomal component. A statistically significant correlation was found between the number of desmosomal components lost and metastasis. Tumours could also be divided into five groups according to their staining for different combinations of cytokeratins. Furthermore, differentiation status as indicated both histologically and by cytokeratin staining correlated with reduced desmosomal staining and metastasis. Tumours were also examined for intensity of staining for the adhesion molecule E-cadherin. Reduction in E-cadherin staining was correlated with mode of invasion and with reduction in desmosomal staining, but not with poor differentiation as indicated by cytokeratin staining. The results of this extensive study reinforce the view that adhesive junctions and adhesion molecules contribute to the suppression of tumour invasion and metastasis.
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PMID:Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour. 966 2

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.
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PMID:Serum concentrations of soluble adhesion molecules in patients with colorectal cancer. 966 59

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


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