Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used antibodies against the alpha subunits of the human fibronectin receptor (FNR) and vitronectin receptor (VNR) to localize simultaneously FNR and VNR at major substrate adhesion sites of fibroblasts and melanoma cells with double-label immunofluorescence microscopy. In early (2-6-h) serum-containing cultures, both FNR and VNR coaccumulated in focal contacts detected by interference reflection microscopy. Under higher resolution immunoscanning electron microscopy, FNR and VNR were also observed to be distributed randomly on the dorsal cell surface. As fibronectin-containing extracellular matrix fibers accumulated beneath the cells at 24 h, FNR became concentrated at contacts with these fibers and was no longer detected at focal contacts. VNR was not observed at matrix contacts but remained strikingly localized in focal contacts of the 24-h cells. Since focal contacts represent the sites of strongest cell-to-substrate adhesion, these results suggest that FNR and VNR together play critical roles in the maintenance of stable contacts between the cell and its substrate. In addition, the accumulation of FNR at extracellular matrix contacts implies that this receptor might also function in the process of cellular migration along fibronectin-containing matrix cables. To define the factors governing accumulation of FNR and VNR at focal contacts, fibroblasts in serum-free media were plated on substrates coated with purified ligands. Fibronectin-coated surfaces fostered accumulation of FNR but not VNR at focal contacts. On vitronectin-coated surfaces, or substrata derivatized with a tridecapeptide containing the cell attachment sequence Arg-Gly-Asp, both FNR and VNR became concentrated at focal contacts. These observations suggest that the availability of ligand is critical to the accumulation of FNR and VNR at focal contacts, and that FNR might also recognize substrate-bound vitronectin.
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PMID:Cell surface distribution of fibronectin and vitronectin receptors depends on substrate composition and extracellular matrix accumulation. 245 33

The identification of specific cell surface glycoprotein receptors for Arg-Gly-Asp-containing extracellular matrix proteins such as fibronectin has focused attention on the role of gangliosides in this process. Is their involvement dependent or independent of the protein receptors? In attachment assays with cells from a human melanoma cell line, titration experiments with an antibody (Mel 3) with specificity for the disialogangliosides GD2 and GD3, used together with a synthetic peptide containing the cell binding sequence Arg-Gly-Asp, show that their joint effect is synergistic. Both the Mel 3 antibody and the synthetic peptide individually cause rapid detachment of melanoma cells from fibronectin substrate but, when used together, much smaller concentrations of both are required to achieve the same effect. The Mel 3 antibody was not nonspecifically reducing receptor binding to the Arg-Gly-Asp sequence since, in binding assays with radiolabeled peptide performed with cells in suspension, very little peptide is bound by the melanoma cells under these conditions but addition of Mel 3, an antibody of IgM isotype, causes a two- to threefold increase in specific binding. The simplest interpretation of these data is that the Mel 3 antibody is causing sufficient clustering of membrane gangliosides in local areas and producing a favorably charged environment to facilitate peptide binding by specific glycoprotein receptors.
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PMID:Synergism between membrane gangliosides and Arg-Gly-Asp-directed glycoprotein receptors in attachment to matrix proteins by melanoma cells. 245 63

The disialogangliosides GD2 and GD3 play a major role in the ability of human melanoma cells to attach to Arg-Gly-Asp-containing substrates such as fibronectin and vitronectin, since pretreatment of these cells with monoclonal antibodies to the oligosaccharide of GD2 and GD3 can inhibit their attachment and spreading on such adhesive proteins. This report demonstrates that human melanoma cells (M21) synthesize and express a glycoprotein receptor that shares antigenic epitopes with the vitronectin receptor on human fibroblasts and is capable of specifically recognizing the Gly-Arg-Gly-Asp-Ser-Pro sequence. Biochemical evidence is presented indicating that the vitronectin receptor on M21 human melanoma cells contains associated calcium and GD2. This ganglioside copurified with the glycoprotein receptor for vitronectin on affinity columns containing either an Arg-Gly-Asp-containing peptide, Concanavalin A, or lentil lectin. This major Arg-Gly-Asp-directed receptor on M21 cells could be metabolically labeled with 45Ca++. Chelation of this ion with EDTA caused the dissociation of GD2 from the receptor and rendered the remaining glycoprotein incapable of binding to an Arg-Gly-Asp containing peptide. Reconstitution experiments demonstrated a requirement for calcium and not magnesium for receptor binding to Arg-Gly-Asp and indicated that addition of ganglioside can enhance this interaction.
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PMID:Human melanoma cell attachment involves an Arg-Gly-Asp-directed adhesion receptor and the disialoganglioside GD2. 247 Jan 10

We have defined the structure of the Osteoclast Functional Antigen (OFA) by immunological and biochemical means. OFA is an abundant surface antigen in human and animal osteoclasts and has been characterized previously by monoclonal antibodies 13C2 and 23C6, one of which mimicks the inhibitory activity of calcitonin on osteoclastic bone resorption. By the following criteria we show that OFA is a member of the integrin family of extracellular matrix receptors and is identical, or at least highly related, to the vitronectin receptor (VNR) previously isolated from placenta and melanoma cells. Immunoprecipitation analysis demonstrates that OFA from osteoclasts and a monkey kidney cell line Vero is a heterodimeric molecule of 140 kD (alpha chain) and 85 kD (beta chain) under nonreducing conditions; on reduction at least one low molecular mass (alpha') species (of approximately 30-kD size) is released, resulting in a 120/100-kD dimer. Immunoblots of OFA isolated from osteoclasts and Vero cells and VNR purified from placenta and probed with heterosera to OFA and monoclonal antibodies to platelet gp111a (VNR beta chain) show immunological cross-reactivity between the alpha chains of OFA and VNR and the use of gp111a as a beta chain by both. OFA from Vero cells binds to an Arg-Gly-Asp containing peptide (GRGDSPPK) isolating a heterodimer recognized by anti-OFA monoclonal antibodies, 13C2 and 23C6. Immunohistochemical analysis showed a similar tissue distribution in humans for the antigen recognized by anti-OFA antibodies, a monoclonal antibody, LM142, raised to melanoma VNR, polyclonal antibodies to the placental VNR and a monoclonal antibody to the presumptive VNR beta chain, platelet glycoprotein 111a. Finally, NH2 terminal amino acid sequencing showed that the amino-terminus of the monkey alpha chain was identical in the 12 assigned residues to that of human VNR alpha chain. The beta chain sequence of OFA differed at least 1 (and up to 4) positions from platelet gp111a (VNR beta) in the first 18 amino acids sequenced. These, and other, data provide the first indication of a function for the VNR and suggest that cell-cell and cell-extracellular matrix interactions involving integrins may play an important role in bone physiology.
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PMID:The osteoclast functional antigen, implicated in the regulation of bone resorption, is biochemically related to the vitronectin receptor. 247 82

The members of the integrin family of membrane glycoprotein heterodimer complexes function as cell surface receptors for adhesive proteins. We report here on the identification of two integrins on the surface of human platelets that bind to thrombospondin. When platelet membrane proteins are radiolabeled with 125I-lactoperoxidase, solubilized in n-octylglucoside, (Boehringer Mannheim Biochemicals, Indianapolis, IN), and applied to a column of thrombospondin-Sepharose, both complexes are bound to the column and specifically eluted with the peptide GRGDSP. One of these integrins, glycoprotein (GP) IIb-IIIa, appears to bind relatively weakly. The second integrin shares the same beta subunit (beta 3 or GPIIIa), but has a distinct alpha subunit that comigrates with the alpha subunit (alpha v) of the vitronectin receptor (VnR) on endothelial cells and reacts with a monoclonal antibody, LM142, which was raised against an integrin from M21 melanoma cells. The alpha v beta 3 integrin is present on a variety of cell types and appears to act as a receptor for thrombospondin on endothelial and smooth muscle cells. On endothelial and M21 melanoma cells this receptor is also involved in adhesion to fibrinogen, vitronectin, and von Willebrand factor (vWF). The alpha v beta 3 integrin is present at approximately equal levels on normal and thrombasthenic platelets, whereas levels of GPIIb-IIIa are greatly reduced on thrombasthenic platelets. The alpha v beta 3 integrin on thrombasthenic platelets also binds to thrombospondin-Sepharose and can be eluted with the peptide GRGDSP. These data indicate that the alpha v beta 3 integrin on platelets, endothelial cells, and smooth muscle cells functions as an Arg-Gly-Asp (RGD)-dependent receptor for thrombospondin.
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PMID:An integrin receptor on normal and thrombasthenic platelets that binds thrombospondin. 169 85

A unique polypeptide containing the repeated structure of core sequence from cell adhesion molecules, poly(Arg-Gly-Asp), was successfully prepared by the polymerization procedure with diphenylphosphoryl azide. This polypeptide dramatically inhibited the aggregation of platelets induced by adenosine diphosphate (ADP) or malignant melanoma cells.
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PMID:Biological activities of synthetic polypeptides containing a repetitive core sequence (Arg-Gly-Asp) of cell adhesion molecules. 248 54

Anti-cell adhesive activity was examined by the synthetic polypeptide, containing repetitive Arg-Gly-Asp sequence of cell attachment site from fibronectin, poly (Arg-Gly-Asp). The attachment of tumour cells to fibronectin substrate was specifically inhibited by adding poly (Arg-Gly-Asp) in cell surface receptor-mediated and divalent cation-dependent manners, but not by unrelated peptides. In our previous study, the lung metastatic formation of tumour cells was dramatically reduced by intravenous co-injection of anti-cell adhesive poly (Arg-Gly-Asp) with B16-BL6 melanoma cells. These findings suggest that polypeptide-mediated inhibition of pulmonary metastasis is partly due to interference with tumour cell adhesion to the substrates including fibronectin in target organs or tissues.
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PMID:Inhibition of tumour cell adhesion by anti-metastatic polypeptide containing a repetitive Arg-Gly-Asp sequence. 248 85

This study sought to determine whether human melanoma cells express integrin-related receptors that mediate their adhesion to laminin. We found that antibodies against the integrin beta 1 chain blocked cell attachment to laminin-coated surfaces. Furthermore, immunofluorescence staining demonstrated beta 1 complexes in vinculin-positive focal adhesion plaques on the basal surface of cells attached to laminin substrates. Chromatography of detergent extracts of 125I-surface-labeled cells on laminin-Sepharose columns recovered two major laminin-binding proteins (100 and 130 kDa, reduced) that bound with high affinity to the columns and were eluted with EDTA. Both proteins were specifically immunoprecipitated from column fractions with monoclonal and polyclonal antibodies to the integrin beta 1 subunit, indicating that they form a noncovalent heterodimer complex. The alpha-like subunit is composed of a 30-kDa light chain that is joined by a disulfide bond to the 100-kDa heavy chain. This complex was not recovered from columns of fibronectin- or collagen type I- or IV-Sepharose. Laminin-binding by the alpha beta 1 complex was independent of Arg-Gly-Asp or Tyr-Ile-Gly-Ser-Arg-like sequences, but required the presence of divalent cations. The 100-kDa alpha-like subunit was electrophoretically and immunochemically distinct from the other known alpha subunits, alpha 1-alpha 6. The results indicate that human melanoma cells express a novel laminin-specific integrin beta 1 complex which may mediate the cells' interactions with this ligand.
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PMID:Human melanoma cells express a novel integrin receptor for laminin. 252 55

1H nuclear magnetic resonance (NMR) spectroscopy was tested for its applicability in evaluating diseased skin. In order to explore potential spectral markers characteristic of diseased tissue, perchloric acid (PCA) extracts of psoriasis and malignant melanoma tissues were compared with normal skin, and changes in melanoma after heat treatment were monitored. In psoriatic plaque extract, the spectral peak intensity ratios of Glu: Ser, creatine: Gly, and taurine: Ala were approximately three-fold compared with symptom-free or normal skin, whereas Val: Leu/Ile was one-half the normal skin ratio. In melanoma extracts, the phosphorylcholine (PC)/glycerophosphorylcholine (GPC): Ala, Glu: Ser, and lactate: Ala ratios were five-, three-, and two-fold higher, respectively, than normal skin and the Val: Leu/Ile ratio was two-thirds of normal skin. With heat treatment, PC/GPC: Ala and Glu: Ser ratios decreased, whereas lactate: Ala and Val: Leu/Ile ratios increased three-fold and one-third, respectively. Results indicate that 1H NMR spectroscopy is a sufficiently sensitive technique to distinguish normal from diseased skin. The main attraction of this technique lies in the possibility of non-invasive study of various skin diseases, malignant transformation of benign tumors, and responses to treatment. Several methodologic problems remain to be resolved before a meaningful interpretation of in vivo observations becomes feasible. Correlation of in vivo and in vitro findings is an essential step toward this goal.
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PMID:1H NMR spectroscopy: an approach to evaluation of diseased skin in vivo. 253 64

Integrin receptors may mediate the adhesion of cells to a number of extracellular matrix components. We found that the attachment of human melanoma cells to collagen types I and IV was blocked by antibodies to the integrin beta 1 subunit but not by peptides containing the Arg-Gly-Asp sequence. Ligand affinity chromatography was used to search for integrin-related receptors which mediate adhesion to native collagens. Detergent extracts of surface 125I-iodinated melanoma cells were chromatographed on type I or IV collagen-Sepharose columns. Bound material was eluted and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. EDTA, but not Arg-Gly-Asp peptides, eluted a mixture of two integrin-related heterodimeric complexes. Each complex contained the integrin beta 1 chain with Mr of 110,000 and a distinct alpha chain with Mr of either 200,000 or 150,000. Immunoprecipitation with specific monoclonal antibodies identified the complexes as very late activation antigen (VLA)-1 (alpha 1 beta 1) and VLA-2 (alpha 2 beta 1), respectively. The binding of these receptors to collagen appeared to be specific because they failed to be retained on fibronectin- or laminin-Sepharose columns. Immunofluorescent staining of cells on collagen substrates with antibodies to VLA-1 and VLA-2 localized these complexes in vinculin-positive adhesion plaques. In contrast, the receptor complexes were not detected in adhesion plaques of cells attached to fibronectin- or laminin-coated substrates. These results indicate that melanoma cells express at least two different integrin-related collagen-binding receptor complexes that appear to mediate cell adhesion to collagen.
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PMID:Identification of integrin collagen receptors on human melanoma cells. 253 53


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