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)

An immunohistochemical analysis for E(epithelial)-cadherin and N(neural)-cadherin expression in relation to tumour angiogenesis was performed in 150 patients with nonsmall cell lung cancer (NSCLC). In all, 71 carcinomas (47.3%) were E-cadherin-negative. Epithelial-cadherin-negative tumours had lymph node metastases significantly more frequently than E-cadherin-positive tumours (P=0.0100). On the other hand, 46 carcinomas (30.7%) were N-cadherin-positive. Regarding tumour vascularity, there was no significant correlation between E-cadherin expression and tumour vascular. In contrast, the frequency of hypervascular tumours was significantly higher for N-cadherin-positive carcinomas than for N-cadherin-negative carcinomas (P=0.0373). Regarding prognosis, the 5-year survival rate of patients with E-cadherin-negative NSCLCs was significantly lower than that of patients with E-cadherin-positive NSCLCs (P=0.0146). In contrast, of the patients with large cell carcinomas, the 5-year survival rate of patients with N-cadherin-positive tumours was significantly lower than that of patients with N-cadherin-negative tumours (P=0.0013). A multivariate analysis demonstrated that E-cadherin status (P=0.0339) and tumour vascularity (P=0.0295) were significant indicators for survival. In conclusion, E-cadherin expression and tumour vascularity are significant prognostic factors of NSCLC patients. Furthermore, N-cadherin expression is associated with tumour angiogenesis, and its expression is one of prognostic factors of patients with large cell carcinomas. Thus, N-cadherin also might play a specific role in undifferentiated large cell carcinomas.
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PMID:Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients. 1277 88

To detect circulating RCC cells, we established a nested RT-PCR system for cadherin-6 mRNA, which is specifically expressed in RCC. A total of 121 samples of peripheral blood (34 healthy volunteers and 87 patients with RCC) were analyzed in this study. Total RNA of the monocyte fraction of the blood was extracted, then nested RT-PCR using specific primers was performed to detect mRNA of N-cadherin or cadherin-6. Nested RT-PCR revealed that expression of cadherin-6 mRNA was not present in the blood of most healthy volunteers (absent in 32/34), but positive expression was observed in the blood at concentrations of 10 cells/ml or greater of the SKRC-33 RCC cell line, which is a strong expresser of cadherin-6. In peripheral blood from patients with metastatic disease, cadherin-6 mRNA was detected in 70.4% (19/27). Messenger RNA of cadherin-6 was detectable in 45.0% (27/60) of patients with localized tumors. The PCR-based detection system for peripheral blood samples from patients with metastatic disease could reveal the presence of circulating RCC cells in the blood. Detection of cadherin-6 mRNA in non-metastatic presurgical RCC patients suggests that careful follow-up study is necessary in these patients.
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PMID:Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma. 1296 85

Both mesotheliomas and renal cell carcinomas can present a wide variety of morphological patterns. Because of this, renal cell carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study was to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and renal cell carcinoma. A total of 48 mesotheliomas (40 epithelioid, 8 sarcomatoid), and 48 renal cell carcinomas (24 conventional, 12 chromophobe, 8 papillary, 4 sarcomatoid) were investigated for the expression of the following markers: calretinin, mesothelin, cytokeratin 5/6, WT1, thrombomodulin (TM), N-cadherin, CD15 (leu-M1), MOC-31, Ber-EP4, BG-8 (Lewis(y)), CD10, renal cell carcinoma marker (RCC Ma), carcinoembryonic antigen (CEA), and B72.3. All (100%) of the epithelioid mesotheliomas reacted for calretinin, mesothelin, and cytokeratin 5/6; 93% for WT1; 78% for TM; 75% for N-cadherin, 48% for CD10, 15% for Ber-EP4, 8% for MOC-31, 8% for RCC Ma, 5% for BG-8, and none for CEA, B72.3, or CD15. Of the sarcomatoid mesotheliomas, 88% expressed calretinin, 75% N-cadherin, 38% CD10, and 13% each expressed cytokeratin 5/6, WT1, and TM. All of the remaining markers were negative. Among the RCCs, 81% expressed CD10, 75% N-cadherin, 63% CD15, 50% RCC Ma, 50% MOC-31, 42% Ber-EP4, 8% BG-8, and 2% TM. The remaining markers were negative. The results indicate that calretinin, mesothelin, and cytokeratin 5/6 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from renal cell carcinomas. The best discriminators among the antibodies considered negative markers for mesothelioma are CD15, MOC-31, and RCC Ma. An accurate differential diagnosis can be reached with the use of any 2 of the 3 recommended positive markers, which should be selected based on availability and on which ones yield the best staining results in a given laboratory. One of the recommended negative markers may be added to the panel if deemed necessary. If confirmation of renal origin is needed, RCC Ma could be useful. Calretinin is the only marker that appears to have any utility in distinguishing between sarcomatoid mesotheliomas and sarcomatoid renal cell carcinomas.
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PMID:The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study. 1518 36

Desmoplastic melanoma is a variant of spindle cell melanoma considered at low risk for distant metastases when compared with other forms of melanoma. The emphasis in the differential diagnosis of desmoplastic melanomas has been placed mostly in distinguishing it from scars and other benign spindle cell proliferations. In contrast, recognizing a subset of desmoplastic melanomas with higher metastatic potential has proven more difficult. We studied the expression of N-cadherin in 21 desmoplastic melanomas. The expression of N-cadherin was examined by immunohistochemistry using archive material and a mouse anti-N-cadherin monoclonal antibody previously shown to react in routinely processed paraffin-embedded tissues. Of 21 cases, N-cadherin was strongly positive in 10, only weakly or focally positive in 3, and negative in 8. Seven of 21 patients had distant metastases, and N-cadherin was strongly positive in 6 of those 7 cases. In contrast, only 1 of 11 patients within the group of N-cadherin-negative or weakly positive tumors had distant metastases. Our results show that strong N-cadherin expression in desmoplastic melanoma correlates with distant metastases and potentially more aggressive behavior. In contrast, desmoplastic melanomas with low metastatic potential are mostly negative or only focally positive for N-cadherin. The data suggest that N-cadherin may be a useful marker in recognizing a subset of desmoplastic melanoma with higher metastatic potential.
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PMID:Differential expression of N-cadherin distinguishes a subset of metastasizing desmoplastic melanomas. 1678 91

Melanoma, the most aggressive form of skin cancer, which accounts for 75% of all skin cancer-related deaths, continues to rise at an alarming rate worldwide. Despite a favorable cure rate when surgically removed at an early stage, the response rate of patients with metastatic disease to single agent chemotherapy is less than 15%, and biologic therapies are only marginally effective. Given this bleak picture, there is a great need to identify and characterize genes that play an important role in the advanced stages of melanoma and thus, may represent valuable targets for clinical therapy. The cell adhesion molecules N-cadherin, MCAM and beta3 integrin have been suggested to represent melanoma progression markers; yet, little is known as to whether they may constitute therapeutic targets for the disease. To provide information regarding this aspect, we determined by way of whole-genome and tissue microarray analysis, their level of expression concordant with melanoma progression, and via RNA interference and antisense technology, their role in melanoma cell proliferation, migration, and invasion. The results of these studies demonstrate that N-cadherin and beta3 integrin expression correlates with progression to advanced-stage melanoma, whereas expression of MCAM does not. On the other hand, MCAM and beta3 integrin are the two adhesion molecules that play a pivotal role in melanoma cell migration and invasion, and for this reason, may represent valuable targets for melanoma therapy.
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PMID:The role of N-cadherin, MCAM and beta3 integrin in melanoma progression, proliferation, migration and invasion. 1696 99

Endothelial cells express two dependent intercellular adhesion molecules: vascular endothelial (VE)-cadherin, specific for endothelial cells, and N-cadherin, also present in neuronal, lens, skeletal and heart muscle cells, osteoblasts, pericytes and fibroblasts. While there exists a vast amount of evidence that VE-cadherin promotes angiogenesis, the role of N-cadherin still remains to be elucidated. We found that a soluble 90-kDa fragment N-cadherin promotes angiogenesis in the rabbit cornea assay and in the chorioallantoic assay when cleaved enzymatically from the extracellular domain of N-cadherin. Soluble N-cadherin stimulates migration of endothelial cells in the wound healing assay and stimulates phosphorylation of extracellular regulated kinase. In vitro experiments with PD173074 and knock-down of N-cadherin and fibroblast growth factor (FGF)-receptor, showed that the pro-angiogenic effect of soluble N-cadherin is N-cadherin- and FGF-receptor-dependent. Our results suggest that soluble N-cadherin stimulates migration of endothelial cells through the FGF-receptor.
Clin Exp Metastasis 2006
PMID:Soluble N-cadherin fragment promotes angiogenesis. 1702 23

The development of a primary tumor as such is not the main cause of death, but is rather the spreading of metastases, which causes over 90% of deaths in cancer patients. This largely depends on the ability of tumor cells to migrate away from the tumor and relocate at other areas of the body. Cell migration is known to be regulated by various extracellular signal substances such as neurotransmitters. However, before single tumor cells can start to invade into distant tissue, they have to dissociate from the primary tumor. This requires the disruption of cell-cell contacts, which are provided by a plethora of adhesion molecules like the family of cadherins. Using our well, established three-dimensional collagen-based cell migration assay, we show that engagement of N-cadherin results in a significant decrease of the spontaneous and the norepinephrine-induced migration of MDA-MB-468 breast carcinoma cells, which was due to an increase in the average break length. Moreover, this N-cadherin driven influence on the migratory activity is intracellularly integrated via multiple signaling pathways. Our results show that the impact of N-cadherin on the locomotion of MDA cells involves the activation of the adenylyl cyclase and the phosphatidylinositol-3-kinase (PI3K), but is independent of the protein kinase C (PKC) alpha. In summary, we provide evidence that the engagement of N-cadherin provides a stop signal for breast carcinoma cell migration, and accordingly the use of anti-N-cadherin antibodies or soluble ligands might be a tool to inhibit metastasis formation in E-cadherin negative but N-cadherin positive tumors.
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PMID:N-cadherin engagement provides a dominant stop signal for the migration of MDA-MB-468 breast carcinoma cells. 1717 Dec 99

N-cadherin is up-regulated in aggressive breast carcinomas, but its mechanism of action in vivo remains unknown. Transgenic mice coexpressing N-cadherin and polyomavirus middle T antigen (PyVmT) in the mammary epithelium displayed increased pulmonary metastasis, with no differences in tumor onset or growth relative to control PyVmT mice. PyVmT-N-cadherin tumors contained higher levels of phosphorylated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) than PyVmT controls, and phosphorylated ERK staining was further increased in pulmonary metastases. Tumor cell isolates from PyVmT-N-cadherin mice exhibited enhanced ERK activation, motility, invasion, and matrix metalloproteinase-9 (MMP-9) expression relative to PyVmT controls. MAPK/ERK kinase 1 inhibition in PyVmT-N-cadherin cells reduced MMP-9 production and invasion but not motility. Furthermore, inactivation of fibroblast growth factor receptor in PyVmT-N-cadherin cells reduced motility, invasion, and ERK activation but had no effect on PyVmT cells. Thus, de novo expression of N-cadherin in mammary ducts enhances metastasis of breast tumors via enhanced ERK signaling.
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PMID:N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation. 1740 17

Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.
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PMID:A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. 1740 56

Most of the melanoma markers used today are melanocytic markers or pigmentation pathway-associated genes driven by the microphthalmia transcription factor, MITF, and include among others, tyrosinase, dopachrome tautomerase, DCT, melan-A and S100B. Genomic studies repeatedly revealed several novel melanoma marker genes including those of the transcription factor NOTCH2, WNT5A, proliferation-associated genes TOPO2A and CDC2, membrane receptors FGFR and EphA3, adhesion molecules N-cadherin, beta3 integrin and syndecan-4, and the cell surface antigens CD59/protectin and MIA. Other genomic analyses tried to define the gene signature of the metastatic disease but failed to find a consistent one except the gold standard genes of beta3 integrin, syndecan-4 and WNT5a. Studies on the gene signatures of chemoresistance and cytokine sensitivity of melanoma clearly defined apoptosis-resistance as one of the key elements of the above biological properties, but the data are controversial, mostly because of the use of inappropriate model systems and the lack of confirmation on clinical samples. Accordingly, application of genomic technologies must be more "translational" to provide breakthrough in melanoma diagnosis and therapy.
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PMID:Melanoma genomics reveals signatures of sensitivity to bio- and targeted therapies. 1743 76


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