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

Adhesion molecules, including integrins, are important for interactions of cancer cells with vessel walls, a step leading to cancer metastasis. Disintegrins block the action of integrins by binding to them. We tested the hypothesis that the disintegrin eristostatin would block metastasis by interfering with cancer cell adhesion to vessel walls, thus preventing extravasation. Experimental metastasis assays, in which B16F1 melanoma cells (controls vs eristostatin-treated, 25 micrograms/ml) were injected via mesenteric veins of anesthetized C57BL/6 mice, showed that eristostatin reduced (P < 0.05) the mean number of liver metastases from 14.4 to 0.6 at 11 days postinjection (p.i.). We examined three different steps in metastasis at which eristostatin could have exerted its effect, namely, cell arrest, extravasation, and migration. Control and eristostatin-treated B16F1 cells were fluorescently labeled and examined by videomicroscopy in liver microcirculation in vivo at various times up to 14 days p.i. Measurements of vessel size in which cell arrest occurred and length/width ratio of arrested cells showed only small differences between control and eristostatin-treated cells. Eristostatin treatment did not prevent extravasation, and the timing and process of extravasation were similar for both treated and control cells; by 3-4 days p.i. more than 90% of the cells had extravasated or were in the process. Eristostatin also did not affect the ability of extravasated cells to migrate through the extracellular matrix to the subcapsular region where tumors later form. Therefore, we conclude that eristostatin exerted its primary effect by regulating the number of individual cancer cells that grow after extravasation.
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PMID:Effects of the disintegrin eristostatin on individual steps of hematogenous metastasis. 764 9

Adhesion to vascular endothelium is a primary step in the colonization of select target organs by blood-borne cancer cells. Previous studies in our laboratory have shown that adhesion is followed by the establishment of fully functional gap junctional channels between the arrested tumor cell and the endothelium and that gap junctional communication might play an important role in extravasation. Here we report on a critical interdependence between endothelial cell adhesion and communication of lung-metastatic cancer cells. Gap junctions are assembled at focal adhesion contacts between tumor cells and endothelial cells where they mediate metabolic coupling between the junction-forming cell pair. The level of coupling depends on sufficient amounts of connexin43 (cx43) protein expression by both cell partners and, in a rate-limiting fashion, on the expression level of the receptor/ligand pair that mediates adhesion between tumor cells and the endothelium. This conclusion is based on our findings that (a) tumor cells with equal cx43 message, yet different adhesion potential for endothelial cells, differ significantly in their level of communication with the endothelium (e.g., R230AC-MET vs. R3230AC-LR), and (b) gap junctional communication between B16-F10 melanoma cells and lung-matrix-modulated endothelium can be effectively blocked by antiadhesive, anti-Lu-ECAM-1 monoclonal antibody 6D3 and by soluble Lu-ECAM-1. Significantly increased adhesion and communication levels in highly lung-metastatic carcinoma cells imply a role of gap junctional coupling in cancer metastasis, presumably by facilitating extravasation.
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PMID:Adhesion-mediated gap junctional communication between lung-metastatatic cancer cells and endothelium. 765 9

Transfection of murine metastatic B78H1 cells (derived from B16 melanoma) with a syngeneic H-2Kb gene was used to study the effect of Major Histocompatibility Complex (MHC) gene products on tumour cell adhesion to endothelial cells and matrix proteins and the involvement in the metastatic process. H-2Kb-expressing transfectants showed a reduced adhesion to endothelial surfaces of different origin (four murine endotheliomas and human umbilical vein endothelial cells) when compared to parental B78H1 cells and to controls transfected with pSV2neo alone. On the average a 50-70% reduction in adhesion to endothelial cells was observed among H-2Kb transfectants. H-2Kb transfectants had a reduced expression of the alpha 4 integrin subunit, moreover the adhesion of Neo-transfected clones to endothelial cells was reduced to the levels of H-2Kb transfectants by antibodies directed against the beta 1 subunit and the endothelial VCAM-1 molecule, thus suggesting an impairment of the VLA-4/VCAM-1 interaction in H-2Kb transfectants. Adhesion to extracellular matrix components was also strongly decreased: in general the adhesion of H-2Kb cells showed a 50-75% inhibition with respect to Neo or parental controls. The highest difference was observed in adhesion to vitronectin and laminin, the lowest in adhesion to fibronectin. Reduction in adhesive properties of H-2Kb-expressing transfectants could be involved in the reduced metastatic ability, evaluated by means of intravenous injection of cells: H-2Kb transfectants yielded less than ten lung colonies, while all controls produced more than 100. Our data indicate that expression of a single class I MHC gene can significantly alter the metastatic phenotype of MHC-negative tumour cells and this could be related to a general alteration of tumour cell adhesive interactions.
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PMID:Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transfected tumour cells. 769 18

Adhesion of tumor cells to endothelial cells is a crucial step in the complex sequence of metastasis. In addition to type and local density of adhesion molecules on both cell types, shear forces exerted by the blood flow have been described to be of major importance in governing cell adhesion. Most of the experiments on the molecular basis of tumor-endothelial cell adhesion have been performed as static assays which lack shear forces. We have developed an artificial venule which shares the following in vivo characteristics. A confluent layer of endothelial cells lines the luminal surface of a glass capillary of 1 mm i.d. with pores of 30 nm diameter to allow diffusion of molecules from outside the capillary. Physiological pressure of 16 mbar, flow rate of 2 cm/s, and shear forces of 2 dynes/cm2 are maintained. This device allowed us to show that under dynamic conditions adhesion of B16 mouse melanoma cells to EA.hy926 endothelial cells is mediated most likely by a lectin-like structure on B16 cells and oligosaccharide(s) on endothelial cells. In addition, endothelial activation-independent adhesion was found to be restricted to only a fraction of endothelial cells, as the number of B16 cells that adhered was independent of the number of B16 cells applied.
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PMID:Tumor cell--endothelium adhesion in an artificial venule. 776 83

Modification of non-immunological cell adhesion properties plays a major role in the decrease in metastatic ability observed after transfection of the H-2Kb gene in H-2-negative B16-derived melanoma clone cells. To investigate the role played by different class-I major histocompatibility complex (MHC) genes on non-immunological properties relevant for metastasis, transfection with the H-2Db gene alone or in conjunction with the H-2Kb gene was performed. H-2Db gene transfection did not modify either metastatic potential or non-immunological cell adhesion properties. Double KbDb transfectants showed a decreased metastatic ability when compared to control clones and to Db transfectants; a decrease in homotypic adhesive ability was also observed, even though not in all clones studied: therefore expression of the Db gene is also relevant. The mechanisms of homotypic cell adhesion were studied and found to be dependent upon temperature and divalent cations. Adhesion was partially inhibited by an antiserum directed against the beta 1 integrin subunit, whereas anti-alpha IIb beta 3 was ineffective. Cell pre-treatment with anti-beta 1 serum reduced metastatic ability. A decreased expression of alpha 4 and alpha 6 integrin subunits was observed in Kb clones, whereas no difference in the levels of some homophilic cell adhesion molecules, such as N-CAM and alpha IIb beta 3, was found. Adhesion required the activity of tyrosine kinases, as suggested by the decreased adhesive properties and impaired metastatic ability of cells pre-treated with the tyrosine-kinase-inhibitor genistein. These results are compatible with involvement of integrin molecules of the beta 1 family in the adhesive ability of these cells. Our data show that: (a) immunological and non-immunological effects of MHC transfection are correlated and depend on the class-I gene used, suggesting that MHC gene therapy can be highly successful only if appropriate MHC genes are transfected; (b) non-immunological cell-adhesion properties modified after MHC transfection could be related to an impairment of integrin-mediated adhesive interactions.
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PMID:H-2Kb and H-2Db gene transfections in B16 melanoma differently affect non-immunological properties relevant to the metastatic process. Involvement of integrin molecules. 792 28

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

Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and its counter-receptor, lymphocyte function associated antigen-1 (LFA-1), play very important roles in immune responses. In this study, the effects of cytokines on cultured human melanoma cells (MMG2) were examined, especially focussing on the expression of ICAM-1 on MMG2 and lymphocyte adhesion to MMG2. Both the expression of ICAM-1 and HLA-DR on MMG2 increased after treatment with IFN-gamma. ICAM-1 expression began to increase earlier than HLA-DR expression. TNF-alpha and IL-1 beta also increased the expression of ICAM-1 on MMG2. However, these cytokines did not increase the expression of HLA-DR. IFN-gamma had a dose dependent effect on lymphocyte adhesion to MMG2. Pretreatment of IFN-gamma treated MMG2 with 84H10 (anti-ICAM-1 antibody) or pretreatment of lymphocytes with either SPV-L7 (anti-LFA-1 alpha antibody) or IOT10 (anti-LFA-1 beta antibody) inhibited the lymphocyte adhesion to MMG2. These results suggest that ICAM-1 molecules induced on melanoma cells by IFN-gamma can interact with LFA-1 molecules on lymphocytes.
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PMID:Intercellular adhesion molecule-1 on cultured human melanoma cells: influence of cytokines. 809 20

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.
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PMID:Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines. 822 94

We compared integrin-mediated adhesion to extracellular matrix (ECM) components of cultured human melanocytes and 6 human melanoma cell lines with different metastatic capacities in nude mice. Cultured melanocytes and most melanoma cell lines adhered strongly to fibronectin (FN), whereas only highly metastatic cell lines adhered to laminin (LM), collagen type I (COI) and type IV (COIV). Adhesion to LM and CO could be blocked by anti-alpha 6 and anti-alpha 2 monoclonal antibodies (MAbs) respectively. This observation is consistent with the finding that expression of LM receptor alpha 6 beta 1 and LM/CO receptor alpha 2 beta 1 was low on melanocytes and non- or poorly metastatic cell lines, whereas these integrins were strongly expressed on highly metastatic cell lines. In addition, immunoprecipitation from [35S]-methionine-labeled cells demonstrated increased synthesis of alpha 6, alpha 2 and beta 1 in highly metastatic cell lines and immunohistochemistry showed expression of alpha 6 beta 1 and alpha 2 beta 1 only in xenograft lesions from highly metastatic cell lines. Furthermore, the observation that adhesion of melanocytes and non- or poorly metastatic cell lines could be stimulated with anti beta 1 MAbs demonstrates that these receptors, on these cells, are expressed in an inactive state. Our results suggest that alpha 2 beta 1 and alpha 6 beta 1 play a role in human melanoma metastasis in nude mice and demonstrate that interactions of these integrins with their ligands can be regulated at the level of surface expression and activation state of the receptor.
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PMID:Regulation of integrin-mediated adhesion to laminin and collagen in human melanocytes and in non-metastatic and highly metastatic human melanoma cells. 838 65

Several cinnamoyl compounds have been shown to have antitumor activities, but not specifically anti-invasive or antimetastatic effects. U-77,863 (o-methyl cinnanamide) was originally isolated from a fermentation beer of Streptomyces griseoluteus and recently synthesized (Harper, DE and Welch DR. Journal of Antibiotics, in press). Based upon some differential activities of cinnanamides, in general, and U-77,863, specifically, we tested the hypothesis that U-77,863 could inhibit invasion and metastasis of human malignant melanoma cell lines C8161 and A375M. Pretreatment of melanoma cells in vitro with nontoxic doses of U-77,863 caused a dose-, and time-dependent, reversible reduction (IC50 = 12.5 micrograms/ml) of invasion through Matrigel-coated polycarbonate filters in the Membrane Invasion Culture System (MICS). Likewise, lung colonization was significantly (P < 0.05) inhibited when tumor cells were pretreated in vitro with U-77,863 prior to intravenous injection. Structure-activity analysis revealed that the acrylamide side-chain alone and cinnanamide were only slightly less potent than U-77,863, whereas cinnamic acid analogs did not inhibit tumor cell invasion at doses < or = 100 micrograms/ml. U-77,863 inhibits invasion and metastasis without decreasing growth rates or clonogenic potential. Adhesion to endothelial monolayers or extracellular matrices (Matrigel) is not affected by exposure to U-77,863. U-77,863 presumably inhibits metastasis by inhibiting tumor cell extravasation (invasion). U-77,863 is a lead compound for developing a novel class of anti-invasive/anti-metastatic drugs.
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PMID:U-77,863: a novel cinnanamide isolated from Streptomyces griseoluteus that inhibits cancer invasion and metastasis. 844 12


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