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)

Invasion is the hallmark of tumor malignancy. We situate invasion within microecosystems comprising neoplastic cells as well as host cells. Modulation of invasion within such systems is ascribed to balances between promoter and suppressor pathways. The E-cadherin/alpha-, beta-, gamma-catenin complex has an invasion-suppressor function as evidenced by transfections either with sense cDNA encoding these molecules or with antisense cDNA inhibiting their expression. Loss of heterozygosity at the E-Cadherin (uvo) locus has been reported, but mutations in the E-cadherin gene seem to be rare. Downregulation of E-cadherin occurred at the level of transcription or of mRNA stability. Ex vivo cultures from invasive tumors or metastases produced cells that were homogeneously E-cadherin-positive and noninvasive in vitro. These observations have led to the idea that factors in the host downmodulate the E-cadherin complex and promote invasion most probably in a transient way.
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PMID:Cancer metastasis: negative regulation by an invasion-suppressor complex. 758 33

E-Cadherin has been shown to be an invasion tumor suppressor gene, but few epidemiological studies have revealed relationships between loss of E-cadherin expression and invasive tumor growth and/or metastasis. The adhesive function of E-cadherin is dependent on the integrity of the catenin components which link E-cadherin to the actin filaments. In order to achieve a better correlation between the loss of cell adhesion and metastasis in cancer, we decided to investigate both E-cadherin and the catenins. 157 archival primary mammary carcinomas were immunohistochemically studied using antibodies against E-cadherin, alpha-, beta- and gamma-catenin. The following results were obtained: (a) Independent of the presence of E-cadherin, loss of expression of one or multiple catenins was noted; (b) loss of E-cadherin and alpha-catenin expression was more pronounced in lobular-type than ductal-type carcinomas; c) axillary lymph node metastases were completely lacking only in the group where expression of E-cadherin, alpha- and beta- catenin was preserved: d) no correlation between expression of c-erbB-2 and E-cadherin or one of the catenins was found. The results demonstrate for the first time that consideration of both the expression of E-cadherin and of the three catenins is useful in evaluation of the metastatic potential of mammary carcinomas.
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PMID:Expression of E-cadherin and catenins in invasive mammary carcinomas. 906 80

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

We have recently characterized a human bladder cancer cell line T24 and a more aggressive lineage related variant of it, T24T. To gain further insights, we have studied their metastatic ability in an in vivo model system. Results show that T24 forms significantly fewer [4/12 (1/11) mice had metastases with 1-2 lesions/mouse] metastasis in SCID/bg mice than T24T [14/14 (6/6) mice had metastases with a mean of 24-28 lesions/mouse]. To begin exploring the mechanisms underlying this difference, we evaluated the mRNA and protein expression levels of metastasis-suppressor genes, known to be important in the progression of other cancers, in our model of bladder cancer progression. A higher mRNA expression of BRMS1, a metastasis suppressor in breast cancer, was observed in T24 cells. In addition, RhoGDI2 mRNA expression was only observed in T24 when compared to T24T, suggesting that Rho activation might play a significant role in the metastatic cascade. However, a basal level mRNA expression of KISS1, described as metastasis suppressor in melanoma and breast, was observed in both the lines and had slightly higher expression in T24T. No difference of Nm23-H1, KAI1, MKK4/SEK1 and E-Cadherin protein levels were noted between these two lines. In summary, it appears that the T24/T24T paired cell lines constitute a useful model for the study of human bladder cancer metastasis that will allow both the discovery and mechanistic evaluation of genes potentially involved in this process.
Clin Exp Metastasis 2000
PMID:The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in lineage related human bladder cancer cell lines. 1159 9

Invasive cell migration in both normal development and metastatic cancer is regulated by various signaling pathways, transcription factors and cell-adhesion molecules. The coordination between these activities in the context of cell migration is poorly understood. During Drosophila oogenesis, a small group of cells called border cells exit the follicular epithelium to perform a stereotypic, invasive migration. We find that the ETS transcription factor Yan is required for border cell migration and that Yan expression is spatiotemporally regulated as border cells migrate from the anterior pole of the egg chamber towards the nurse cell-oocyte boundary. Yan expression is dependent on inputs from the JAK/STAT, Notch and Receptor Tyrosine Kinase pathways in border cells. Mechanistically, Yan functions to modulate the turnover of DE-Cadherin-dependent adhesive complexes to facilitate border cell migration. Our results suggest that Yan acts as a pivotal link between signal transduction, cell adhesion and invasive cell migration in Drosophila border cells.
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PMID:Function of the ETS transcription factor Yan in border cell migration. 1601 14

The reproductive hormone, estrogen, contributes to the development of breast cancer by binding to the estrogen receptor (ER) in the nucleus, triggering cell growth and tumor promotion. In addition to its role in regulating target genes and signaling pathways involved in cell cycle progression, the ER-signaling pathway may regulate the expression of chromatin-remodeling gene, Metastasis-associated 3 (MTA3), or interact with chromatin-remodeling protein, Metastasis-associated 1 (MTA1). The invasion-suppressor gene, E-Cadherin (E-Cad), has recently been identified as a downstream target gene regulated by the ER-MTA3 pathway via the transcriptional repressor, Snail, and the ER-MTA3-Snail-E-Cad pathway has therefore been evoked to explain the clinical observation that ER expression in breast cancer is generally associated with a better clinical outcome. Since E-Cad may play an initiating role during breast tumorigenesis, we hypothesized that this ER-signaling pathway may also determine susceptibility to breast cancer, and examined this in a multigenic case-control study of 468 incident breast cancer patients and 470 healthy controls by genotyping the single nucleotide polymorphisms (SNPs) in five genes (ER, MTA3, Snail, E-Cad, and MTA1) in the ER-signaling pathways. Support for this hypothesis came from the observations that (a) with the exception of Snail, which interacted differently with reproductive risk factors in relation to breast cancer risk, there was a joint effect of the SNPs of these genes and estrogen-related risk factors (age at first full-term pregnancy and obesity, measured by the body mass index) on breast cancer risk (p < 0.05); (b) a trend toward increased risk of developing breast cancer was seen in women harboring a greater number of putative high-risk genotypes of these genes in ER-signaling pathways; (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to have experienced higher estrogen level, i.e., obese women; and (d) the risk effect conferred by obesity was only significant in women with a higher number of putative high-risk genotypes of the ER-signaling genes. These epidemiological findings highlight the role of newly identified novel ER-related pathways in breast cancer development and provide a more comprehensive picture of the tumorigenic effect of estrogen in breast cancer development.
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PMID:Breast cancer risk associated with genotypic polymorphism of the genes involved in the estrogen-receptor-signaling pathway: a multigenic study on cancer susceptibility. 1650 42

Nm23 is a metastasis suppressor gene. In this report, we transfected nm23-H1 cDNA into L9981, a human large cell lung cancer cell line with nm23 negative expression, and made a stable transfectant. L9981-nm23-H1 cells exhibited lower cells proliferation rate, more G0/G1 phase growth and an increase in apoptosis with a dramatic decreased in the tumor cells ability to metastasize. L9981-nm23-H1 cells also demonstrated a significantly reduced lymph node and pulmonary metastatic capacity in vivo when injected into the nude mice. Furthermore, we used DNA microarray analysis to explore the change in expression of the metastasis-related genes in L9981-nm23-H1 cells. We found that the expression of beta-Catenin, E-Cadherin and TIMP-1 were significantly increased while expression MMP-2, CD44v6, and VEGF was dramatically decreased in L9981-nm23-H1, as confirmed by RT-PCR and western blot. These results demonstrated that nm23-H1 can suppress the mobility and metastatic capacity of cancer cells and the molecular mechanism by which nm23-H1 suppresses tumor metastasis may be via increasing the expression of metastasis-related genes such as beta-Catenin, E-Cadherin and TIMP-1 and decreasing the expression of MMP-2, CD44V6 and VEGF.
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PMID:Transfection of nm23-H1 increased expression of beta-Catenin, E-Cadherin and TIMP-1 and decreased the expression of MMP-2, CD44v6 and VEGF and inhibited the metastatic potential of human non-small cell lung cancer cell line L9981. 1716 24

E-Cadherin (CDH1) expression is reduced in thyroid carcinomas by primarily unknown mechanisms. In several tissues, SNAIL (SNAI1) and SLUG (SNAI2) induce epithelial-mesenchymal transition by altering target gene transcription, including CDH1 repression, but these transcription factors have not been studied in thyroid carcinoma. Recently, our group has provided direct evidence that ectopic SNAI1 expression induces epithelial and mesenchymal mouse tumors. SNAI1, SNAI2, and CDH1 expression were analyzed in thyroid-derived cell lines and samples of human follicular and papillary thyroid carcinoma by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The effect of SNAI1 expression on CDH1 transcription was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting in ori-3 cells. Thyroid carcinoma development was analyzed in CombitTA-Snail mice, in which SNAI1 levels are up-regulated. SNAI1 and SNAI2 were not expressed in cells derived from normal thyroid tissue, or in normal human thyroid samples, but were highly expressed in cell lines derived from thyroid carcinomas, in human thyroid carcinoma samples, and their metastases. SNAI1 expression in ori-3 cells repressed CDH1 transcription. Combi-TA mice developed papillary thyroid carcinomas, the incidence of which was increased by concomitant radiotherapy. In conclusion, SNAI1 and SNAI2 are ectopically expressed in thyroid carcinomas, and aberrant expression in mice is associated with papillary carcinoma development.
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PMID:Snail family transcription factors are implicated in thyroid carcinogenesis. 1772 39

Anti-angiogenic drugs, alone or in combination with chemotherapeutics, are increasingly used by medical oncologists. In many cases, however, their mechanism of action and the tailoring of optimal dosage/schedule are still elusive. Circulating endothelial cell (CEC) and progenitor (CEP) number and viability are modulated in a large series of diseases including cancer, and look promising as surrogate biomarkers for the definition of the optimal biological dose of anti-angiogenic drugs and for patients' stratification. Along with CECs and CEPs, potential EC- and CEP-related surrogate molecular markers such as VE-Cadherin and CD133 are currently under preclinical and clinical investigation.
Cancer Metastasis Rev 2008 Mar
PMID:Chemotherapy and the tumor microenvironment: the contribution of circulating endothelial cells. 1806 48

The cadherin molecules at adherens junctions have multiple isoforms. Cadherin isoform switching (cadherin switching) occurs during normal developmental processes to allow cell types to segregate from one another. Tumor cells often recapitulate this activity and the result is an aggressive tumor cell that gains the ability to leave the site of the tumor and metastasize. At present, we understand some of the mechanisms that promote cadherin switching and some of the pathways downstream of this process that influence cell behavior. Specific cadherin family members influence growth-factor-receptor signaling and Rho GTPases to promote cell motility and invasion. In addition, p120-catenin probably plays multiple roles in cadherin switching, regulating Rho GTPases and stabilizing cadherins.
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PMID:Cadherin switching. 1832 69


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