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)

Integrins from the very late activation antigen (VLA) subfamily are involved in cellular attachment to extracellular matrix (ECM) proteins and in intercellular adhesions. It is known that the interaction of integrin proteins with their ligands can be regulated during cellular activation. We have investigated the regulation of different VLA-mediated adhesive interactions through the common beta 1 chain. We have found that certain anti-beta 1 antibodies strongly enhance binding of myelomonocytic U-937 cells to fibronectin. This beta 1-mediated regulatory effect involved both VLA-4 and VLA-5 fibronectin receptors. Moreover, anti-beta 1 mAb also induced VLA-4-mediated binding to a recombinant soluble form of its endothelial cell ligand VCAM-1. Non-activated peripheral blood T lymphocytes, unable to mediate VLA-4 interactions with fibronectin or VCAM-1, acquired the ability to bind these ligands in the presence of anti-beta 1 mAb. The anti-beta 1-mediated changes in the affinities of beta 1 integrin for their ligands were comparable to those triggered by different lymphocyte activation agents such as anti-CD3 mAb or phorbol ester. Adhesion of melanoma cells to other ECM proteins such as laminin or collagen as well as that of alpha 2-transfected K-562 cells to collagen, was also strongly enhanced by anti-beta 1 mAb. These beta 1-mediated regulatory effects on different VLA-ligand interactions do not involve changes in cell surface membrane expression of different VLA heterodimers. The anti-beta 1-mediated functional effects required an active metabolism, cytoskeleton integrity and the existence of physiological levels of intracellular calcium as well as a functional Na+/H+ antiporter. Beta 1 antibodies not only increased cell attachment but also promoted spreading and cytoplasmic extension of endothelial cells on plates coated with either fibronectin, collagen, or laminin as well as induced the rapid appearance of microspikes in U-937 cells on fibronectin. Moreover, both beta 1 integrin and the cytoskeletal protein talin colocalized in the anti-beta 1 induced microspikes. These results emphasize the central role of the common beta 1 chain in regulating different adhesive functions mediated by VLA integrins as well as cellular morphology.
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PMID:Regulation of the VLA integrin-ligand interactions through the beta 1 subunit. 137 69

Adhesion molecules are substances which are involved in the interactions between cells, and between cells and the extracellular matrix in both benign and malignant tissues. Two members of this group--intercellular adhesion molecule-1 (ICAM-1) and MUC18--have previously been found to be expressed on melanoma; however, studies seeking a correlation between expression and metastatic behaviour have yielded conflicting results. In this study we investigated the expression of these two antigens and that of a number of other adhesion molecules [VCAM-1, ELAM, and the neural cell adhesion molecule (NCAM)] on a range of benign and malignant melanocytic lesions. Both ICAM-1 and MUC18 were found on a high percentage of all melanocytic lesions including benign naevi. VCAM-1 was found to be expressed on 79 per cent of benign naevi, 62 per cent of primary melanomas less than 1.5 mm in depth, and 6 per cent of thick primaries. The antigen was present on 14 per cent of lymph node metastases and on no extranodal deposits. This suggests that loss of melanoma cell adhesion mediated by VCAM-1 may be important in the development of metastatic melanoma.
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PMID:A study of adhesion molecules as markers of progression in malignant melanoma. 137 91

Human melanoma is a highly metastatic cancer and the regional lymph nodes are generally the first site of metastasis. Adhesion to cryostat sections of human lymph nodes was therefore studied using two human melanoma models established from lymph node metastases, namely, MeWo cell lines of diverse metastatic potentials and a highly metastatic cell line of recent origin designated MIM/8. We found a good correlation between the metastatic potentials of the melanoma cells as measured in nude mice and their ability to adhere to cryostat sections of human lymph nodes. When adhesion to immobilized extracellular matrix proteins was measured, a significant increase in adhesion, which correlated with increased metastasis, was seen mainly on vitronectin and to a lesser extent on fibronectin. The adhesion to vitronectin and to the frozen sections were specifically blocked by an RGD-containing peptide, mAb 661 to vitronectin and mAb LM609 to integrin alpha v beta 3. FACS analysis revealed a significant and specific increase in cell surface expression of alpha v beta 3 on the metastatic cells as compared to the parent line. Together these results suggest that the adhesion of melanoma cells to lymph node vitronectin via the alpha v beta 3 receptor plays a role in the process of lymphatic dissemination.
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PMID:Human melanoma cells derived from lymphatic metastases use integrin alpha v beta 3 to adhere to lymph node vitronectin. 138 72

A panel of monoclonal antibodies (mAbs) to bovine fibronectin (FN) is described which modulates either heparin binding or cell adhesion to FN, or both. A combination of competitive exclusion and binding to proteolytic fragments identified epitopes in the Hep II, Hep III/I and CBF (cell binding fragment) regions of FN. mAb A17, which bound to the CBF region, strongly inhibited the cell adhesion of BHK-21 fibroblasts, primary corneal fibroblasts and endothelial cells, and NM4 mammary adenocarcinoma cells, to FN at mAb concentrations as low as 1 microgram/ml. This mAb was not so effective at inhibiting the adhesion of B16 mouse melanoma cells. Adhesion of B16 cells to FN was more sensitive to inhibition by mAbs binding to Hep II (A2, A9, A32, A35). Of these, A32 and A35 significantly increased the binding of 35S-heparin to FN, whereas A2 and A9 did not affect it. mAbs A2, A9 and A32 showed good binding to HBF, the 40 kDa proteolytic fragment of human FN which contains both Hep II and IIICS (type III connecting segment). These mAbs inhibited B16 cell adhesion to the HBF (heparin binding fragment) by 30-50%, the greatest inhibition being shown by mAb A32. Two synthetic peptides from the HBF, CS1 (peptide 1) from the IIICS region and peptide I from the Hep II region, also inhibited B16 cell adhesion to HBF by approximately 70 and 30%, respectively. These results suggest that maximal cell adhesion to the HBF involves both CS1 and Hep II. The inhibitory effects of the two peptides were linearly additive in combination, whereas the inhibitory mAbs A2, A9 and A32 showed synergistic additive effects with each of the peptides. This points to the existence of an additional important cell binding site in Hep II, other than peptide I. Recent independent evidence for an additional cell binding site in Hep II supports this view. Melanoma cellular receptor(s) for the Hep II region may be cell surface proteoglycans but do not appear to bind to areas of Hep II with high affinity for soluble heparin, as the latter was not an inhibitor of B16 cell adhesion to the HBF. The increased effectiveness of A32 in inhibiting cell adhesion, compared to A2 and A9, may be due to conformational effects which increase the binding of soluble heparin, but reduce affinity for the cellular receptor. These results are discussed in context with other reports in the literature.
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PMID:Anti-fibronectin antibodies that modify heparin binding and cell adhesion: evidence for a new cell binding site in the heparin binding region. 138 58

A laminin-binding peptide (peptide G), predicted from the cDNA sequence for a 33-kDa protein related to the 67-kDa laminin receptor, specifically inhibits binding of laminin to heparin and sulfatide. Since the peptide binds directly to heparin and inhibits interaction of another heparin-binding protein with the same sulfated ligands, this inhibition is due to direct competition for binding to sulfated glycoconjugates rather than an indirect effect of interaction with the binding site on laminin for the 67-kDa receptor. Direct binding of laminin to the peptide is also inhibited by heparin. This interaction may result from contamination of the laminin with heparan sulfate, as binding is enhanced by the addition of substoichiometric amounts of heparin but inhibited by excess heparin and two heparin-binding proteins. Furthermore, laminin binds more avidly to a heparin-binding peptide derived from thrombospondin than to the putative receptor peptide. Adhesion of A2058 melanoma cells on immobilized peptide G is also heparin-dependent, whereas adhesion of the cells on laminin is not. Antibodies to the beta 1-integrin chain or laminin block adhesion of the melanoma cells to laminin but not to peptide G. Thus, the reported inhibition of melanoma cell adhesion to endothelial cells by peptide G may result from inhibition of binding of laminin or other proteins to sulfated glycoconjugate receptors rather than from specific inhibition of laminin binding to the 67-kDa receptor.
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PMID:Interactions of a laminin-binding peptide from a 33-kDa protein related to the 67-kDa laminin receptor with laminin and melanoma cells are heparin-dependent. 138 42

Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1----4Glc beta 1----Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin-based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of "cascade" reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells.
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PMID:Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells. 151 64

The CD36 and ICAM-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for Plasmodium falciparum-infected erythrocytes (IRBC). Adhesion of IRBC from Thai patients with uncomplicated and severe falciparum malaria to purified CD36 or ICAM-1 and to C32 melanoma cells was compared. All malaria isolates bound to solid phase-adsorbed CD36 and to fluid-phase 125I-labeled CD36. IRBC adhesion to purified ICAM-1 varied widely, and no correlation with clinical severity of disease was observed. The cytoadherent phenotype of IRBC was modulated by selective panning on plates coated with purified CD36 or ICAM-1. IRBC selected by panning on CD36+, ICAM-1+ melanoma cells bound to cells that express surface CD36 but not to CD36-deficient cells, indicating that CD36 exerts a strong selective pressure on the IRBC cytoadherent phenotype. IRBC adhesion to CD36 and ICAM-1 suggests that P. falciparum parasites may use these receptors in vivo to promote parasite survival and immune evasion.
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PMID:Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. 171 52

Activation of endothelial cells by the two inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor strongly increases tumor cell adhesion. We describe antibody inhibition studies showing that the endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell-surface glycoprotein selectively expressed by cytokine-activated endothelial cells and responsible for neutrophil adhesion, is the major, if not the only, mediator of colon carcinoma cell adhesion to activated endothelial cells. Among the different tumor cell lines tested, seven colon carcinoma cell lines were sensitive to ELAM-1 antibodies. Adhesion of melanoma, osteosarcoma, and lung, cervix, or kidney carcinoma cell lines to IL-1-treated endothelial cells was not affected by the ELAM-1 antibody. This result suggests that ELAM-1 is selectively recognized by colon carcinoma cells and that adhesion of tumor cells to activated endothelial cells could be mediated by different and specific mechanisms.
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PMID:Tumor cell adhesion to endothelial cells: endothelial leukocyte adhesion molecule-1 as an inducible adhesive receptor specific for colon carcinoma cells. 171 24

The effect of pretreatment of metastatic B16 melanoma cells with 10(-6) M all trans-retinoic acid resulted in a significant inhibition of lung colonization following injection of 10(5) cells into the tail vein of syngeneic C57BL mice. Adhesion of melanoma cells to vascular endothelial cell monolayers, and subendothelial extracellular matrix was also inhibited by pretreatment with retinoic acid, as was tumour cell aggregation following seeding of pretreated cells on to 0.5% agar. Release of 35SO4 from radiolabelled subendothelial extracellular matrix by melanoma cells was essentially unaltered by retinoic acid pretreatment, as was the release of radiolabel from [3H]proline-labelled matrix, while plasminogen activator activity was enhanced in retinoic-acid-treated cells. These observed changes in adhesive properties may be responsible, at least in part, for the retinoic-acid-induced inhibition of lung colonization.
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PMID:Retinoic acid-induced inhibition of metastatic melanoma cell lung colonization and adhesion to endothelium and subendothelial extracellular matrix. 173 48

Phorbol esters which activate protein kinase C (PKC) have been shown to enhance experimental lung metastasis. Therefore, it was reasoned that inhibitors of PKC might also modulate metastasis. We have investigated this possibility using a PKC inhibitor, MDL 27,032 [4-propyl-5(4-pyridinyl)-2(3H)-oxazolone], as well as staurosporine and H-7. Treatment of B16F1 murine melanoma cells with MDL 27,032 for 24 h in culture and subsequent i.v. injection of the cells into mice resulted in greater than 90% inhibition of lung metastasis. Inhibition of metastasis was time dependent, with 90% of maximum inhibition occurring by 8 h of incubation. The 50% inhibitory concentration (IC50) for inhibition of metastasis with MDL 27,032 was 7 microM, a value similar to that for the inhibition of B16F1 membrane-associated PKC (IC50 = 13 microM) but not cytosolic PKC (IC50 = 54 microM). B16F1 cells treated with MDL 27,032 for 24 h were less adherent than untreated cells to extracellular matrix/basement membrane proteins. Adhesion to fibrinogen and collagen IV was inhibited (IC50 = 6 microM and 48 microM, respectively) by MDL 27,032, whereas adherence to laminin and fibronectin was not affected, indicating that the drug affects specific adhesion molecules. MDL 27,032-treated cells were also found to be less adherent than untreated cells to human umbilical vein endothelial cells. The phosphorylation of an 80-kDa B16F1 cell plasma membrane protein was stimulated under conditions known to stimulate PKC activity, and MDL 27,032 inhibited this phosphorylation in a dose-dependent manner. MDL 27,032 was more potent than H-7 for the inhibition of metastasis but was significantly less potent than staurosporine. These results support the hypothesis that there is a critical role for PKC-mediated phosphorylation of cell surface adhesion receptors in metastasis.
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PMID:Inhibition of experimental metastasis and cell adhesion of B16F1 melanoma cells by inhibitors of protein kinase C. 173 79

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