UMLS:C0001511 - FACTA Search

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Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer metastasis poses the greatest challenge to the eradication of malignancy. The majority of clinical and experimental evidence indicates that metastasis is a non-random, organ-specific process. Tumor cell interaction with endothelium and subendothelial matrix constitutes the most crucial factor in determining the organ preference of metastasis. A plethora of cell surface adhesion molecules, which encompass four major families (i.e., integrins, cadherins, immunoglobulins and selectins) and many other unclassified molecules, mediate tumor-host interactions. Adhesion molecules and adhesion processes are involved in most, if not all, of the intermediate steps of the metastatic cascade. Decreased E-cadherin expression and increased CD44 expression are clearly correlated with the acquisition of the invasive capacity of primary tumor cells. Similarly, altered expression pattern of many other adhesion molecules such as upregulated expression of the laminin receptors and depressed expression of fibronectin receptors (alpha 5 beta 1) appears to be involved in tumor cell invasion into the subendothelial matrix. Tumor cell-endothelium interactions involve several well-defined sequential steps that can be analyzed by the 'Docking and Locking' hypothesis at the molecular level. Tumor cell-matrix interactions are determined by the repertoire of adhesion receptors of tumor cells and the unique composition of organ-specific matrices. Our experimental data, together with others', suggest that the integrin alpha IIb beta 3 is one of the major players in these tumor-host interactions. Tumor-host interaction is a dynamic process which is constantly modulated by a host of factors including various cytokines, growth factors and arachidonate metabolites such as 12(S)-HETE. Delineation of the molecular mechanisms of tumor-host interactions may provide additional means to intervene in the metastatic process.
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PMID:Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. 142 22

E- and P-cadherin are calcium (Ca2+)-dependent cell adhesion molecules important in the morphogenesis and maintenance of skin structure. By use of flow cytometry and specific antibodies, we now show that cultured human melanocytes express E- and P-cadherin on their surfaces, and that these molecules have the same characteristics as reported for other cell types. Specifically, melanocyte cadherins are sensitive to trypsin digestion in the absence of Ca2+ and are protected from trypsin degradation by Ca2+, and are functional at 37 degrees C but not at 4 degrees C. We further show that melanocytes contain mRNA transcripts encoding both E- and P-cadherin. Adhesion of cultured melanocytes to keratinocyte monolayers is abolished by pre-treatment of the melanocytes with trypsin/EDTA, which degrades E- and P-cadherins, is greatly reduced by anti-E-cadherin antibodies and is slightly reduced by antibodies to P-cadherin, alpha 2, alpha 3 and beta 1 integrins. In contrast to normal melanocytes, eight of nine melanoma cell lines lacked E-cadherin (or expressed markedly reduced levels) and five were negative for P-cadherin. Melanoma cells also failed to adhere to keratinocyte monolayers. These results demonstrate that normal human melanocytes express functional E- and P-cadherin and that E-cadherin is primarily responsible for adhesion of human melanocytes to keratinocytes in vitro. In addition, transformed melanocytes express markedly reduced levels of E- and P-cadherin, and exhibit decreased affinity for normal keratinocytes in vitro, suggesting that loss of cadherins may play a role in melanoma metastasis.
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PMID:E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro. 805 51

We report here on the consequences of reducing the expression of EP-cadherin at the earliest stages of Xenopus development. Injection of oligodeoxynucleotides antisense to maternal EP-cadherin mRNA into full-grown oocytes reduced the mRNA level in oocytes, and the protein level in blastulae. Adhesion between blastomeres was significantly reduced, as seen in whole embryos, and in assays of the ability of blastomeres to reaggregate in culture. This effect was especially conspicuous in the inner cells of the blastula and included the disruption of the blastocoel. The severity of the EP-cadherin mRNA depletion and of the disaggregation phenotype was dose dependent. This phenotype was rescued by the injection into EP-cadherin mRNA-depleted oocytes of the mRNA coding for a related cadherin, E-cadherin, that is normally expressed at the gastrula stage in the embryonic ectoderm.
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PMID:A functional test for maternally inherited cadherin in Xenopus shows its importance in cell adhesion at the blastula stage. 811 31

Adhesion molecules are thought to play a vital role in the induction and maintenance of tissue differentiation and their loss or down-regulation has been implicated in the neoplastic process. Recent studies have shown that the morphoregulatory activities are a consequence of interactive processes between several cell adhesion molecules rather than the function of a single molecule. Therefore, we have investigated a panel of adhesion molecules including members of the integrin, cadherin and immunoglobin superfamily in colorectal cancer. Twenty-eight consecutive colorectal adenocarcinomas were stained using an avidin-biotin indirect immunoperoxidase technique. Our results showed a consistent loss of the alpha 2 and beta 1 integrin subunits (21/28 = 75% and 22/28 = 78.6% respectively) and a decrease in expression of E-cadherin in 5/5 poorly differentiated adenocarcinomas. Carcinoembryonic antigen expression was preserved but with basolateral accentuation seen in tumours. There was no statistical correlation with Dukes' stage. These results provide further evidence that in colorectal cancer there is a widespread deregulated expression of cell-cell and cell-matrix adhesion molecules. Changes in the expression and function of adhesion molecules which regulate growth and differentiation may play a role in the behaviour of colorectal cancer.
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PMID:Loss of cell-cell and cell-matrix adhesion molecules in colorectal cancer. 835 41

It is now clear that adhesive interactions play a critical role in the process of metastatic tumor dissemination. Adhesion molecules act as both positive and negative modulators of the metastatic process. Molecules such as E-cadherin that promote homotypic tumor cell adhesion function to maintain intercellular contacts that confine cells to the primary tumor site and are negatively correlated with metastatic potential. Because tumor cells are rapidly eliminated from the circulation, those cells that can quickly arrest in the vasculature at a secondary site and pass through the vessel wall into the surrounding tissue will have a selective advantage toward establishing new metastatic colonies. The first step in this process is specific adhesion to venular endothelial cells in selected organs, a process mediated by tumor cell surface molecules such as Sialyl LewisX or the VLA-4 (alpha 4 beta 1) integrin that mediate binding to endothelial adhesion molecules such as the E-selectin or the vascular cell adhesion molecule, VCAM-1. Site-specific endothelial determinants such as the lung endothelial cell adhesion molecule, LuECAM, may additionally specify particular sites for preferential adhesion and subsequent site-specific metastasis of particular tumor types. After adherence to endothelial cells and subsequent endothelial retraction, metastatic tumor cells must adhere to elements of the subendothelial basement membrane such as laminin and types IV and V collagen, interactions frequently mediated by members of the beta 1 and beta 4 integrin families. Finally, metastatic tumor cell adhesion to connective tissue elements such as fibronectin, type I collagen and hyaluronan, mediated by molecules such as the beta 1 integrins and by the CD44 cell surface adhesion molecule, are required for movement of tumor cells into the subendothelial stroma and subsequent growth at these new sites. Thus, metastatic potential can be influenced both positively and negatively by a variety of cell surface adhesive molecules that act both independently and in concert to direct tumor cells to particular tissues, allowing them to arrest in those tissues, migrate across the vessel wall and grow at the secondary site. In the current review, I discuss the nature of the adhesion molecules that have been implicated in the metastatic process, emphasizing those molecules that have been shown to correlate with metastasis in clinical human tumors or that have been shown to influence metastatic potential in in vivo experimental assays.
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PMID:Adhesion molecules in tumor metastasis. 840 Jan 43

Adhesion molecules such as integrins and cadherins are thought to play a critical role in T-cell migration and localization within the epidermis (epidermotropism). The purpose of this study was to correlate T-cell expression of the integrin CD103 and E-cadherin in cutaneous T-cell lymphoma (CTCL). Serial sections of skin biopsies from 22 patients with CTCL and 13 with benign reactive dermatitis were stained with antibodies to CD4, CD103, and E-cadherin by the avidin-biotin peroxidase technique. CD103 was expressed on single epidermotropic CD4+ T-cells in 9/9 early stage (patch/plaque) CTCL and 6/10 reactive dermatitis biopsies. Less than 30% of dermal T-cells expressed CD103. All 4/4 late stage (tumor) CTCL were CD103-. Epidermal aggregates of CD4+ T-cells (Pautrier's microabscesses) were CD103-. E-cadherin was expressed on epidermal keratinocytes and follicular and sweat gland epithelia but not on T-cells. We conclude that CD103 expression on cutaneous T-cells parallels the degree of epidermotropism exhibited in both neoplastic and inflammatory disorders of the skin. E-cadherin is not expressed on T-cells infiltrating the skin. Further investigation is necessary to further elucidate the interaction between CD103 and E-cadherin in facilitating trafficking of T-cells into the epidermis.
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PMID:The role of alpha E beta 7 integrin (CD103) and E-cadherin in epidermotropism in cutaneous T-cell lymphoma. 886 17

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 889 33

Adhesion molecules play an important role in organogenesis, would healing, inflammation, and progression of malignant tumors. Three major classes of adhesion molecules may be discriminated by function: (a) calcium-dependent homotypic adhesion molecules (e.g. cadherins), (b) substrate adhesion molecules (e.g. integrins) and (c) heterotypic adhesion molecules (e.g. ICAM-1). Molecules of each of the three classes have been identified in urologic tumors. Results of research on substrate adhesion molecules and heterotypic adhesion molecules have not yet led to new clinical concepts. In contrast, loss of E-cadherin in tumors of the bladder and prostate has been clearly associated with de-differentiation of tumors and diminished survival of patients. Loss of another adhesion molecule, C-CAM, has been observed in prostate cancer. This has led to new therapeutic approaches, which are in an experimental stage at present. It may be expected that, in the future, new therapeutic concepts will be based on research on adhesion molecules in urologic tumors.
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PMID:[Adhesion molecules in urologic tumors]. 899 27

Adhesion of Langerhans cells (LC) to keratinocytes is mediated by E-cadherin. IL-1, TNF-alpha, and LPS mobilize LC from epidermis and presumably attenuate LC-keratinocyte adhesion. To determine whether these mediators modulated LC E-cadherin-dependent adhesion directly, we characterized their effects on LC-like dendritic cells expanded from murine fetal skin (FSDDC). FSDDC were propagated from day 16 C57BL/6 fetal skin and isolated as aggregates (FSDDC-A) in which homophilic adhesion was mediated by E-cadherin. IL-1, TNF-alpha, and LPS induced dissociation of FSDDC-A that began within 4 to 8 h and was complete within 20 h. Anti-IL-1RI mAb inhibited disaggregation caused by IL-1alpha and IL-1beta, but not that induced by TNF-alpha or LPS. Anti-TNF-alpha mAb inhibited the effect of TNF-alpha and LPS, but not that caused by IL-1alpha or IL-1beta. Flow cytometry of FSDDC-A revealed that IL-1, TNF-alpha, and LPS induced increased expression of MHC class II, CD40, and CD86 and decreased E-cadherin expression that was temporally related to dissociation of aggregates. IL-1 and TNF-alpha caused a rapid reduction in FSDDC E-cadherin mRNA levels that preceded the decrease in E-cadherin surface expression. These results demonstrate that cytokines that induce LC emigration in vivo act directly on LC-like cells in vitro, reduce E-cadherin mRNA levels, down-regulate E-cadherin surface expression, and induce a loss of E-cadherin-mediated adhesion.
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PMID:Regulation of E-cadherin-mediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo. 955 17

Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our laboratory. They proliferated in suspension culture without aggregation in a complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced cell-cell and cell-surface adhesion. In this study, we explored the mechanism of this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting a role for E-cadherin. However, there were no changes in the expression of E-cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1 than did untreated cells. To examine the possibility that the adhesion of these cells might be induced by decreased MUC1 expression, the level of MUCI expression was directly reduced using an antisense oligonucleotide. The MUC1 antisense oligonucleotide induced cell-cell and cell-surface adhesion of these breast cancer cells, just as NaB did. Our observations indicate that E-cadherin can be functionally suppressed by overexpression of MUC1 but resumes its activity after suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy for cancer therapy.
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PMID:Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines. 958 47

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