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

Adhesion to specific extracellular matrix molecules appears to be an important prerequisite for successful target organ colonization by metastasizing tumour cells. Interference in the adhesive function of malignant cells with antiadhesive agents is therefore one potential approach for preventing metastasis. Recently, synthetic peptides taken from the cell interaction sites of fibronectin have been characterized as inhibitors of cellular adhesion in vitro. Using these antiadhesive probes we have examined the role of cell adhesion to fibronectin in tumour metastasis using the B16-F10 murine melanoma model system. Two sequences from the IIICS cell-binding domain, the 25-mer CS1 peptide and the tetrapeptide Arg-Glu-Asp-Val (REDV), had no detectable activity, but the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS), an active sequence from the central cell-binding domain, exhibited potent, dose-dependent inhibition, indicating a role for this cell recognition determinant in tumour metastasis. Under appropriate conditions GRGDS treatment afforded remarkable protection to the host; mice injected with melanoma cells and peptide were still alive 15 months after injection whereas mice injected with melanoma cells alone died within six weeks. Kinetic analyses of the retention of tumour cells in the lungs and of the vascular clearance rate of labelled GRGDS predict an early time frame of activity for the peptide. From the results of a variety of in vitro invasion and migration assays it appears that GRGDS may interfere with multiple, fibronectin-mediated adhesive and migratory events at different points of the metastatic cascade. In preliminary studies designed to optimize the therapeutic usefulness of GRGDS-like agents, peptide conjugates have been found to possess enhanced antiadhesive activity as well as an extended vascular clearance rate. In the future, therefore, these or related peptide derivatives may be potentially useful agents for the prevention of tumour metastasis.
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PMID:The cell interaction sites of fibronectin in tumour metastasis. 285 15

Many hemopoietic cell lines were examined for their ability to adhere to culture dishes coated with extracellular matrix proteins. Adhesion assay was performed with murine and human leukemic cell lines representative of different stages of differentiation along both erythroid and myeloid lineages. All the hemopoietic cell lines tested adhered to fibronectin but not to laminin, types I, III, and IV collagen, serum-spreading factor, and cartilage proteoglycans. In addition to immortalized cell lines, immature erythroid and myeloid mouse bone marrow cells adhered to fibronectin. To define the fibronectin region involved in hemopoietic cell adhesion, proteolytic fragments, monoclonal antibodies, and synthetic peptides were used. Among different fibronectin fragments tested, only a 110-kD polypeptide, corresponding to the fibroblast attachment domain, was active in promoting adhesion. Moreover, a monoclonal antibody to the cell binding site located within this domain prevented hemopoietic cell adhesion. Finally, the tetrapeptide Arg-Gly-Asp-Ser, which corresponds to the fibronectin sequence recognized by fibroblastic cells, specifically and competitively inhibited attachment of hemopoietic cells to this molecule. The cell surface molecule involved in the interaction of mouse hemopoietic cells with fibronectin was identified as a 145,000-D membrane glycoprotein by adhesion-blocking antibodies. This glycoprotein was found to be antigenically and functionally related to the GP135 membrane glycoprotein involved in the adhesion of fibroblasts to fibronectin (Giancotti, F. G., P. M. Comoglio, and G. Tarone, 1986, Exp. Cell Res., 163:47-62). On the basis of these data, we conclude that interaction of hemopoietic cells with fibronectin involves a specific fibronectin sequence and a 145,000-D cell surface glycoprotein. We speculate that this property might be relevant for the interaction of hemopoietic cells with the bone marrow stroma, which represents the natural site of hemopoiesis.
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PMID:Fibronectin-plasma membrane interaction in the adhesion of hemopoietic cells. 294 50

Soluble fibronectin binds specifically to glycoprotein (GP) IIb-IIIa on thrombin-activated platelets, and this binding is not observed with platelets of patients with Glanzmann's thrombasthenia (GT) which lack GPIIb-IIIa. Here we report that GT platelets retain the ability to interact with fibronectin-coated surfaces. Adhesion to fibronectin does not require platelet activation and is inhibited by soluble fibronectin, antibodies specific for fibronectin, peptides containing the sequence Arg-Gly-Asp and polyclonal antibodies specific for band 3 of the chicken embryo fibroblast fibronectin receptor (anti-band 3). Using anti-band 3, we have purified a second fibronectin receptor from human platelets, a heterodimer composed of glycoproteins previously designated GPIc and GPIIa. The GPIc-IIa complex is found on both GT and normal platelets and appears to be identical to the GP138 kD-GP160 kD complex recently immunopurified by Giancotti et al. (1986. Exp. Cell Res. 163:47-62) and by Sonnenberg et al. (1987. J. Biol. Chem. 268:10376-10383). In this report, we provide the first evidence that GPIc-IIa actually mediates adhesion of platelets to fibronectin-coated surfaces. GPIc-IIa thus represents a second functional fibronectin receptor, distinct from GPIIb-IIIa, that is largely responsible for the adhesion of nonactivated platelets to fibronectin-coated surfaces.
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PMID:Glycoprotein Ic-IIa functions as an activation-independent fibronectin receptor on human platelets. 296 81

We have used a rat neural cell line, B65, to investigate the relative contributions of gangliosides and glycoprotein receptors in adhesion to fibronectin. Monoclonal antibodies against two neuroectoderm-associated gangliosides, D1.1 and GD3, inhibit the rate of B65 attachment to fibronectin, suggesting that these gangliosides are involved in the adhesion process. Adhesion to fibronectin is not affected by a third monoclonal antibody against a separate, unidentified cell-surface component of B65 cells. Furthermore, B65 cells lacking D1.1 adhere to fibronectin at a slower rate than B65 cells that express D1.1. The involvement of glycoprotein receptors in adhesion is demonstrated by the ability of antibodies against human fibronectin receptor to inhibit B65 attachment to fibronectin. In addition, adhesion is blocked by a hexapeptide containing the Arg-Gly-Asp fibronectin sequence which is necessary for binding to the receptor. Trypsin treatment of B65 cells in the absence of divalent cations results in proteolysis of the fibronectin receptor with an accompanying loss of ability of the cells to attach to fibronectin. D1.1 and GD3 expression is not affected by this trypsinization, indicating that the gangliosides alone are incapable of mediating attachment. The glycoprotein receptors must be primarily responsible for adhesion to fibronectin with the gangliosides playing a secondary role as enhancers or modulators.
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PMID:Involvement of gangliosides and glycoprotein fibronectin receptors in cellular adhesion to fibronectin. 296 13

Platelets adhere to vitronectin substrate following activation with physiological concentrations of thrombin. Adhesion of activated platelets to vitronectin substrate is dependent upon the presence of divalent cations, the amount of vitronectin, and the duration of adhesion assay. The adhesion of platelets is inhibited by synthetic peptides containing the sequence of Arg-Gly-Asp. In addition, monoclonal antibodies to glycoprotein IIb-IIIa complex inhibit the adhesion of activated platelets to vitronectin substrate in a dose-dependent manner. These studies suggest that the glycoprotein IIb-IIIa complex on activated platelets may interact with vitronectin substrate through the Arg-Gly-Asp mechanism. Since vitronectin is present in the subendothelial matrix, it might be involved in platelet-vessel wall interactions.
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PMID:Interaction of thrombin-stimulated platelets with vitronectin (S-protein of complement) substrate: inhibition by a monoclonal antibody to glycoprotein IIb-IIIa complex. 323 53

Stem cell factor (SCF) or c-kit ligand is a growth factor cytokine produced by stromal cells that is known to influence mast cell proliferation and differentiation. We hypothesized that SCF may also influence the adhesion of mast cells to connective tissue matrix. To examine this hypothesis, we stimulated MCP5/L mast cells or murine bone marrow-derived cultured mast cells (BMCMC) with either SCF or PMA and observed adhesion to fibronectin (FN). As expected, 80 to 90% of PMA-activated MCP5/L cells or BMCMC adhered to FN. In addition, SCF promoted MCP5/L cell or BMCMC adhesion to FN in a dose-response fashion with 50 to 60% of BMCMC adhering to FN at a concentration 10 ng/ml of SCF. BMCMC adhesion was observed with as little as 200 pg/ml of SCF. Adhesion of SCF stimulated BMCMC to FN did not require IL-3, but was dependent on the concentration of FN used to coat the assay surface. Mast cell adhesion in the presence of SCF appeared to occur through an integrin receptor as adhesion was calcium dependent and could be blocked by an RGD (Ang, Gly, Asp)-containing peptide. SCF did not directly mediate adhesion through interaction with c-kit, as FN-coated surfaces exposed to SCF before initiation of the adhesion assay did not promote adhesion in the absence of soluble SCF. Rather, SCF appeared to stimulate adhesion to FN by activating mast cells through its interaction with c-kit. Thus, antibody to SCF blocked adhesion, and rat and murine SCF stimulated BMCMC adhesion to FN, but human SCF, which does not bind to murine c-kit, did not stimulate adhesion. Genistein, which inhibits tyrosine kinase activity, partially inhibited SCF-induced adhesion. SCF thus stimulates mast cell adhesion and, because SCF is produced normally in tissues, it may be a major factor responsible for the adhesion of mast cells to connective tissue matrix under physiologic conditions.
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PMID:Stem cell factor induces mast cell adhesion to fibronectin. 750 10

The integrin supergene family includes receptors for a variety of extracellular matrix as well as cell surface proteins. Integrin alpha 4 has been shown to play an important role in leukocyte adhesion and extravasation during immune and inflammatory reactions. One recognition sequence known to interact with alpha 4 is the Leu-Asp-Val (LDV) site contained in the connecting segment 1 region of fibronectin. Here we present evidence that shows that a conformationally restricted RGD-containing peptide is a potent inhibitor of cell adhesion mediated by alpha 4 beta 1, a receptor not convincingly documented to interact with RGD peptides. This peptide, 1-adamantaneacetyl-Cys-Gly-Arg-Gly-Asp-Ser-Pro-Cys (disulfide bridge between residues 1-8), blocks Jurkat cell adhesion to connecting segment 1-containing peptides as well as cell adhesion to cytokine-activated endothelial cells. Adhesion of Jurkat cells to either vascular cell adhesion molecule-expressing cells or recombinant vascular cell adhesion molecule-coated plates was likewise inhibited by this peptide. Furthermore, alpha 4 beta 1 can bind directly to a cyclic RGD peptide immobilized to Sepharose. Integrins, alpha 5 beta 1, alpha v beta 3, alpha IIb/beta IIIa, alpha 2 beta 1, alpha v beta 1, alpha v beta 5, alpha v beta 6, and alpha 3 beta 1, have been shown to recognize the Arg-Gly-Asp (RGD) sequence present in a variety of extracellular matrix proteins, and our data support the addition of alpha 4 beta 1 to this group. Further studies using molecular modeling of such cyclic RGD peptides could help in the design of more potent peptides or nonpeptide mimetics that could effectively block alpha 4-mediated activity and have potential application in a number of inflammatory diseases.
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PMID:Cyclic RGD peptide inhibits alpha 4 beta 1 interaction with connecting segment 1 and vascular cell adhesion molecule. 751 41

Cell-substratum adhesion plays a crucial part in the cascade of events that control growth or turn on and consummate a differentiation program. We are investigating the molecular basis of oligodendrocyte (OLG) cytodifferentiation, employing pure cultures of OLGs isolated from postmyelination brains. We have shown that such OLGs will regenerate in vitro and reenact the ontogenic development of myelin, but to do so they need a signal. Adherence to a polylysine surface in the presence of 20% horse serum generates such a signal. Among the events that are turned on upon OLG adhesion is the phosphorylation of myelin basic protein; no such phosphorylation takes place in the non-adhered cell. We postulated that horse serum provides an adhesion molecule. Laminin, fibronectin, collagen and native vitronectin failed to replace horse serum. Hence, we set out to fractionate horse serum by screening with an adhesion assay. We report here the identification, purification and partial characterization of a novel, heparin-binding horse serum glycoprotein that we have termed Glycine-Rich Adhesion Serum Protein--GRASP--to stress the fact that this protein has a high content of glycine and functions, in vitro, as an adhesion molecule for OLGs. There is 61% similarity at the N-terminus between GRASP and histidine-rich glycoprotein precursor (HRGP), an alpha 2-glycoprotein from human plasma. However, our data suggest that GRASP is not the horse serum homolog of HRGP. First, the two Gps are functionally distinct: HRGP does not promote the adhesion of OLGs. Second, the amino acid compositions differ significantly, e.g., GRASP is not histidine- but rather glycine-rich. Third, the region of sequence similarity between GRASP and HRGP is conserved throughout the cystatin superfamily. Fourth, anti-Gp55 polyclonal Abs recognize a similar set of polypeptides--save for slight differences in M(r)-in human serum as in horse serum, indicating that HRGP and GRASP are two distinct but related proteins and are both present in human and horse sera. GRASP is a dimer trimer of seemingly identical subunits of M(r) approximately 55,000 ; the native protein has an M(r) x 10(-3) approximately 120-140, of which 24-27% is contributed by carbohydrate. Using GRASP as a substratum allows the growth of OLGs in serum-free medium. GRASP is as good an effector of myelin basic protein phosphorylation as 20% horse serum. We conjecture that the mechanism of GRASP function features: 1) exposure of a cryptic sequence--after a change in conformation induced upon binding to polylysine--with affinity for an OLG signal-transducing receptor; and 2) interaction of its heparin-binding domain with OLG surface heparin sulfate proteoglycans and/or the aforementioned receptor.
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PMID:GRASP: a novel heparin-binding serum glycoprotein that mediates oligodendrocyte-substratum adhesion. 753 46

Demonstration of murine mast cell adhesion to fibronectin (FN) following PMA-mediated cell activation raised the question whether crosslinking of high affinity IgE receptors on mouse mast cells might induce changes in adhesiveness of these cells to FN. Murine mast cells of line MCP5/L were used to investigate the effect of antigenic stimulation on cell adhesion to fN and mediator secretion. effect of antigenic stimulation on cell adhesion to FN and mediator secretion. Adhesion assays were performed using sensitized radiolabeled cells and FN- or BSA-coated 96-well plates. The presence of antigen in the concentrations up to 10 ng/ml resulted in concentration-dependent adhesion potentiation, which was detectable after 5 min, reached maximum at 30 min and persisted or decreased over the next 30 min. Adhesion potentiation decreased at antigen excess and was abolished by heat inactivation of IgE in the antiserum prior to cell treatment. External calcium ion and temperature dependence of adhesion together with the observation that RGD (Arg, Gly, Asp)--containing peptide blocked cell binding to FN suggests that FC epsilon RI crosslinking-induced adhesion potentiation involves an integrin type receptor on cell surface. Sensitized mast cells allowed to adhere spontaneously to FN released more histamine and beta-hexosaminidase upon antigen challenge. Hence, the results show the relations between IgE-induced mast cell activation, adhesion to FN and mediator secretion.
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PMID:Relations between Fc epsilon RI crosslinking-induced mast cell activation and adhesion to fibronectin. 753 25

We have discovered a cryptic cell-adhesion domain in non-muscle myosin II heavy chain. A 205 kDa cell-adhesion-promoting polypeptide (p205) was extracted from BHK cells by Nonidet P-40 or Dounce homogenization. Adhesion to p205 was specifically inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro, indicating a role for the Arg-Gly-Asp cell-adhesion motif. Purified p205 was identified as non-muscle myosin II heavy chain, based on sequence analysis and on the cross-reactivity of p205 with anti-(bovine trachea myosin) antibodies. Further experiments showed that the heavy chain of purified myosin II has cell-adhesion-promoting activity in a cell-blotting assay, and cross-reacted with anti-p205 antibodies. Finally, the adhesion domain was located in the tail portion of myosin II heavy chain, where an Arg-Gly-Asp-containing sequence can be found.
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PMID:Non-muscle myosin II heavy chain has a cryptic cell-adhesion domain. 762 21


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