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 have previously reported the isolation of a 66 kDa melanoma-associated antigen, identified by autologous antibody, in serum and unfractionated spent tissue culture media by Western blot analysis. The antigen, detected by autologous serum S150, was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma and head and neck carcinoma cell lines. S150 did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, autologous cultured lymphocytes or fetal calf serum. To further characterize the antigen, spent tissue culture media, obtained from autologous melanoma cell line, Y-Mel 84:420, was separated by an isoelectric focusing column. Unabsorbed control serum S150 was noted to have a maximum titer of 1:2040 against autologous melanoma cells as measured by protein A hemadsorption. Following isoelectric focusing the greatest decrease in autologous antibody titer (30-fold) occurred with fractions having a pI between 2 and 3. Further resolution of the antigen was accomplished with high-pressure ion-exchange chromatography. One of these fractions showed a significantly higher concentration of antigen and was distinctly resolved from bulk serum albumin. Subsequent Western blot analysis, with autologous antibody, of the isolated antigen-containing fraction, confirmed the presence of a single 66 kDa band. Exposure of the antigen, purified by high-pressure ion-exchange chromatography, to neuraminidase ablated recognition by autologous antibody and suggests that sialic acid is present on the protein and may be part of the antigenic epitope. Binding of antigen, obtained following DEAE anion exchange chromatography, was noted to lectins derived from Triticum vulgaris, Dolichos biflorus and Lycopersicon esculentum. Preparative purification of the antigen was accomplished by anion exchange followed by lectin affinity chromatography with a Dolichos biflorus column. Antigen obtained following lectin affinity chromatography subjected to SDS-PAGE and silver stain revealed a single band at 66 kDa. We conclude that a melanoma-associated antigen detected by autologous antibody in spent tissue culture media is an unusually acidic glycoprotein (pI 2-3).
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PMID:Purification and partial characterization of a shed 66 kDa melanoma-associated antigen identified by autologous antibody. 193 77

The ICAM-1 glycoprotein, one of the major cellular adhesion molecules, exhibits a diverse and highly regulated tissue distribution. To better understand the regulatory mechanisms underlying its particular expression pattern, we have cloned the ICAM-1 gene from human leukocyte libraries. By hybridization with various DNA probes derived from different regions of the ICAM-1 cDNA, several clones were identified and isolated. Clone HWB 3R1, containing a 15kb DNA insert, was selected for further characterization. The HWB 3R1 clone hybridized with probes corresponding to the 3' as well as the 5' region of the ICAM-1 cDNA and gave rise to ICAM-1 expression after transfection into the ICAM-1 deficient MJP17 melanoma cell line. The identity of the expressed ICAM-1 was verified by reaction with five different monoclonal antibodies specific for ICAM-1. Sequence analysis of about 1.2kb of DNA around the ATG start codon revealed putative binding sites for various transcription factors situated in the 5' untranslated region as well as within the first intron. These include SP-1, AP-1 and NF-kB binding sites as well as interferon and retinoic acid responsive elements.
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PMID:Structural characteristics of the 5' region of the human ICAM-1 gene. 198 3

Recombinant human tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived, non-glycosylated (17 kDa) peptide that has a remarkably broad range of biological and immunological effects including antiviral action and cytotoxic and cytostatic effects. TNF-alpha was coupled to murine antibody ZME-018, which recognizes a 240 kDa glycoprotein present on over 80% of melanoma cells. The crosslinking was accomplished using the heterobifunctional crosslinking reagent, N-succimindyl 3-(2-pyridyldithio)proprionate (SPDP). After purification on gel-permeation and affinity columns, the resulting eluate was analyzed by non-reducing SDS-PAGE, which confirmed that the product was a mixture of ZME-018 coupled to one or two TNF-alpha molecules. The ZME-TNF conjugate was titered against murine L-929 cells to demonstrate the presence of active TNF. ELISA of the conjugate against target BRO human melanoma cells or non-target T-24 cells demonstrated specific binding only to target cells. Melanoma BRO cells were killed by the immunoconjugate (IC50 of 10 units/mL), whereas native TNF-alpha had no effect at concentrations greater than 50,000 units/mL. The immunoconjugate and TNF-alpha were inactive against T-24 non-target cells. These studies suggest that the sensitivity of cells to TNF was dramatically augmented by specific antibody mediated delivery to tumor cells.
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PMID:Antibody-mediated delivery of tumor necrosis factor (TNF-alpha): improvement of cytotoxicity and reduction of cellular resistance. 198 45

Receptor-mediated recognition and adhesion to laminin, a specific glycoprotein from basement membranes, exert an important role in many biological phenomena. Studying cell surface proteins of B16-F10, a metastatic murine melanoma cell line, we identified a 120-140 kDa glycoprotein (gp120/140) that binds laminin. This glycoprotein was recognized by a polyclonal antibody raised against the human fibronectin receptor beta 1-integrin chain, as well as immunoprecipitated by an anti-alpha 6 chain (monoclonal antibody GoH3), characterizing it as an alpha 6/beta 1-integrin. Its binding to laminin was specific and displayed moderate affinity, as its apparent dissociation constant was 18 nM. To characterize the influence of carbohydrate moieties on the laminin-gp120/140 interaction, metaperiodate oxidation, metabolic inhibition of glycosylation, and enzymatic deglycosylation studies were performed. Our results indicate that gp120/140 Asn-linked oligosaccharides play a part in this interaction. Reciprocally, both metaperiodate and N-glycanase treatment of native laminin reduced its binding to gp120/140, characterizing the latter as a lectin-like molecule. These results point to glycosylation processes as a possible mechanism for variable binding specificity profiles among integrins.
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PMID:Asn-linked oligosaccharide-dependent interaction between laminin and gp120/140. An alpha 6/beta 1 integrin. 199 8

To determine whether isolates of Plasmodium falciparum have intrinsically different cytoadherent properties and whether these differences contribute to the clinical severity of human falciparum malaria, we studied the cytoadherence to C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally acquired infections in Thailand. Parasitized erythrocytes adhere to these melanoma cells principally via the glycoprotein CD36, which is also expressed on most vascular endothelium. In vitro cytoadherence was significantly greater for isolates from patients with biochemical evidence of severe malaria. The cytoadherent properties of P. falciparum parasites may thus be a virulence factor in human falciparum malaria. However, there was no correlation between the degree of in vitro cytoadherence and cerebral symptoms, which suggests that other receptors and/or host factors may be important in the adherence of malaria parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor, interleukin-1, and gamma interferon, which have been implicated in the pathogenesis of cerebral malaria and are known to promote intercellular adhesion in other systems, did not enhance the cytoadherence of P. falciparum isolates to C32 melanoma cells.
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PMID:Clinical correlates of in vitro Plasmodium falciparum cytoadherence. 199 37

Thrombospondin (TS) is a modular adhesive glycoprotein that contains three domains previously implicated in the attachment of cells to TS. These include the amino-terminal heparin-binding domain, the carboxy terminal cell or platelet-binding domain, and an RGDA sequence of TS. We have characterized a mAb against human TS, designated A4.1, which inhibits the attachment of human melanoma cells (G361) to TS. The epitope for A4.1 lies within the amino terminal half of the central stalklike region of TS which is distinct from the three known cell attachment sites. This region of TS is recovered in a 50-kD peptide after chymotryptic digestion of TS in EDTA. It contains the procollagen-like domain of TS as well as three type I repeats of a 60-residue segment homologous to two malarial proteins and the complement proteins properdin, and factors C6 through C9. The purified chymotryptic fragment is an effective attachment factor for G361 cells. A4.1 blocks adhesion to the 50-kD domain, as do some sulfated glycoconjugates. RGD (and RGE) peptides and mAbs against other domains of TS are not inhibitory. Peptides (19 mers) based on the core homology sequence of the three type I repeats of TS are potent attachment factors for these cells, and this adhesion is also inhibited by sulfated glycoconjugates. A polyclonal antibody raised against one of these peptides inhibits adhesion of G361 cells to the peptides, to the 50-kD fragment and to intact TS. Thus a new cell-adhesion site has been identified in TS whose sequence is very similar to the site identified in region II of the circumsporozoite protein of malaria parasites (Rich, K. A., F. W. George IV, J. L. Law, and W. J. Martin. 1990. Science (Wash. DC) 249:1574-1577. Thus there may be a common receptor which binds TS, malarial proteins, and properdin.
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PMID:The properdin-like type I repeats of human thrombospondin contain a cell attachment site. 199 54

CD63 is a 53-Kd lysosomal membrane glycoprotein that has been identified as a platelet activation molecule. The current study presents evidence that CD63 and Pltgp40, a platelet membrane glycoprotein identified in this laboratory, are the same molecule and that CD63/Pltgp40 is identical to the well-characterized, stage-specific melanoma-associated antigen ME491. Identity of CD63 and Pltgp40 was demonstrated by immunoprecipitation and sequential immunodepletion studies, which showed that the anti-Pltgp40 monoclonal antibody (MoAb) H5C6 and an anti-CD63 MoAb CLB/Gran 12 recognized the same 40- to 55-Kd platelet glycoprotein. In addition, the anti-CD63 MoAb specifically recognized immunoaffinity-purified Pltgp40. Amino acid sequences obtained from NH2-terminal and tryptic fragment peptides of Pltgp40 were used to generate complementary DNA (cDNA) probes using the polymerase chain reaction (PCR) technique. A 386-bp cDNA probe partially encoding CD63/Pltgp40 and a full length cDNA probe were 100% identical to the corresponding sequence of ME491. Antibodies H5C6 and CLB/Gran12 immunoprecipitated a 30- to 60-Kd heterodisperse glycoprotein from G361 melanoma cells, as had previously been reported for antibodies recognizing ME491. These data, taken together with the extensive homology recently reported between ME491, the Schistosoma mansoni membrane antigen SM23, CD37, the tumor-associated antigen CO-029, and the target of an antiproliferative antibody-1, suggest that CD63 is a member of a new family of related molecules.
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PMID:CD63/Pltgp40: a platelet activation antigen identical to the stage-specific, melanoma-associated antigen ME491. 207 66

beta-All-trans retinoic acid (RA) treatment of murine S91-C2 melanoma cells decreases in vitro growth and modulates the glycosylation of specific cellular and cell-surface glycoproteins. The effect of RA treatment on [3H]fucose, [3H]galactose, and [3H]glucosamine incorporation was investigated by metabolic labeling followed by analysis of labeled cellular glycoproteins using polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS-PAGE) and fluorography. RA treatment dramatically increased the incorporation of the labeled monosaccharides into one glycoprotein of Mr 160,000 (gp160), which has been previously implicated in the growth-inhibitory effect of RA on these cells. Following RA treatment, cell-surface sialic acid residues on gp160 were also more intensely labeled by NaIO4 oxidation and subsequent NaB[3H]4 reduction than were those on gp160 of untreated cells. The activities of fucosyl- and galactosyltransferase increased about 1.5 to 1.9 times after RA treatment. These results suggest that the increased activities of the two glycosyltransferases is responsible for the increased incorporation of fucose and galactose into gp160.
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PMID:Modulation by all-trans retinoic acid of glycoprotein glycosylation in murine melanoma cells: enhancement of fucosyl- and galactosyltransferase activities. 211 Aug 61

Surface galactosyltransferase (GT) has been described on a variety of cells where it is believed to be involved in cell-cell and cell-substratum adhesion. Here we show that B16 metastatic murine melanoma cells exhibit a 5-fold higher cell surface GT activity than their nonmetastatic counterparts, although total GT activity in NP-40 solubilized cells is similar for both melanoma variants. Interestingly, on living cells, this cell surface GT almost exclusively galactosylates an endogenous glycoprotein (Mr = 110,000). This metastasis-associated GT is specific for terminal D-N-acetylglucosamine, catalyzes the formation of a beta 1-4 linkage, does not recognize polylactosaminoglycans, and has its specificity altered from D-N-acetylglucosamine to D-glucose by alpha-lactalbumin; yet the Mr = 110,000 protein is not a major substrate when exogenous bovine GT is used on the outside of living cells. In addition to this protein-specific endogenous GT activity, another cell surface GT activity that selectively galactosylates glucosylceramide is also prominent. Endogenous galactosylation of both protein and glycolipid substrates is reduced when the membrane is solubilized by the detergent NP-40 but remains unaltered in the presence of digitonin, which permeabilizes but does not dissolve the membrane. These data suggest that the GTs and their substrates are associated on the cell surface. Chloroquine treatment of intact cells leads to a 4-fold and a 3-fold increase in galactosylation of the Mr = 110,000 protein and glucosylceramide, respectively, suggesting that these two substrates normally reside mostly in the lysosomal or Golgi compartments. The increased expression of lysosomal membrane proteins on the surfaces of highly metastatic cells may, in part, also explain the galactosylation differences observed. These studies further suggest that increased surface localization of certain glycosyltransferases with highly restricted in situ substrate specificities may be a common feature of highly metastatic tumor cells.
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PMID:Metastasis-associated murine melanoma cell surface galactosyltransferase: characterization of enzyme activity and identification of the major surface substrates. 212 34

Tumor cells attach, degrade, and migrate through basement membranes as they metastasize. Laminin, a major glycoprotein of basement membranes, promotes the metastatic activity of tumor cells by stimulating the attachment and migration of the cells and their secretion of collagenase IV. We have identified a synthetic peptide of 19 amino acids (Cys-Ser-Arg-Ala-Arg-Lys-Gln-Ala-Ala-Ser-Ile-Lys-Val-Ala-Val-Ser-Ala-Asp -Arg) from the sequence of the A chain of laminin that increases experimental metastases of the lungs by murine melanoma cells. The peptide is active when injected either intravenously or intraperitoneally. The peptide increased collagenase IV activity, a key enzyme in the breakdown of basement membranes, to the same extent as laminin. This peptide represents an active site on laminin for promotion of the metastatic phenotype and generates a probe for studying the regulation of malignant activities.
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PMID:Identification of an amino acid sequence from the laminin A chain that stimulates metastasis and collagenase IV production. 215 66


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