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)

The role of the transferrin homologue, melanotransferrin (p97), in iron metabolism has been studied using the human melanoma cell line, SK-MEL-28, which expresses this antigen in high concentrations. The mechanisms of iron and transferrin uptake were investigated using human transferrin labelled with iodine-125 and iron-59. Internalised and membrane-bound iron and transferrin were separated using the proteinase, pronase. The uptake of iron from transferrin occurred by at least two processes. The first process was saturable and consistent with receptor-mediated endocytosis, involving internalisation of transferrin bound to specific binding sites. Uptake of iron also occurred by a second process which was non-saturable up to 0.06 mg/ml (0.75 microM) and was of higher efficiency than the saturable process. This process of iron uptake may be the dominant one at physiological serum transferrin concentrations. A membrane-bound, pronase-sensitive, temperature-dependent, iron-binding component was also identified. The number of binding sites was estimated to be approx. 340,000 per cell (assuming 2 atoms of iron per site) and it is suggested that this binding component may be melanotransferrin.
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PMID:The uptake of iron and transferrin by the human malignant melanoma cell. 236 14

MPP+, an oxidative metabolite of a neurotoxin, MPTP, was found to be cytotoxic to human melanoma cell lines, HMV-II and SK-MEL-44. After 3 days of culture in the presence of MPP+, a larger amount of MPP+ was accumulated in HMV-II cells than in SK-MEL-44 cells, which correlated well with the melanin contents; HMV-II cells contain larger amounts of melanin than SK-MEL-44 cells. After 6 days of culture in the presence of MPP+, the cytotoxicity of MPP+ on these cell types was evaluated by counting cell numbers with the dye exclusion test and double-layer soft agar clonogenic assay. It was found that exposure to MPP+ reduced the survival of HMV-II cells more significantly than that of SK-MEL-44 cells. In HMV-II cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to elucidate the mechanism of MPP+ lethality. The formazan formation was reduced markedly by the presence of MPP+ at concentrations much lower than those required for cell death. These results suggest that cytotoxicity of MPP+ may be ascribed to its accumulation due to high affinity for melanin, and to inhibition of the enzymes utilizing ubiquinone in the mitochondrial respiratory chain.
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PMID:Cytotoxic effect of 1-methyl-4-phenylpyridinium ion on human melanoma cell lines, HMV-II and SK-MEL-44, is dependent on the melanin contents and caused by inhibition of mitochondrial electron transport. 239 Feb 89

Tumor necrosis factor (TNF) induces the synthesis of two proteins of Mr 42 and 36 kDa in human fibroblasts and SK-MEL-109 melanoma cells. To identify these proteins, a lambda gt10 cDNA library was prepared from the mRNA of TNF-treated SK-MEL-109 cells. By screening this library, we found a cDNA that preferentially hybridized to TNF-induced RNA. Hybrid-selected mRNA was translated into a protein of 42 kDa; cDNA sequence analysis followed by a comparison with other known protein sequences identified this protein with plasminogen activator inhibitor, type-2 (PAI-2). After removal of TNF, PAI-2 mRNA turned over rapidly, with an apparent half-life of approximately 2.5 h. Addition of dexamethasone increased the turnover of this mRNA, suggesting that the level of PAI-2 mRNA could be regulated post-transcriptionally by glucocorticoids. PAI-2 was not secreted, but accumulated in fibroblasts continuously treated with TNF.
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PMID:Plasminogen activator inhibitor type-2 is a major protein induced in human fibroblasts and SK-MEL-109 melanoma cells by tumor necrosis factor. 239 77

The IgM monoclonal antibody G10 was raised against the human squamous cell carcinoma (SCC) cell line UM-SCC-1. In initial screening against cultured cells, G10 bound to 2 SCC lines (UM-SCC-1 and UM-SCC-13) and 1 pancreatic carcinoma line (UM-PAd-1) but not to cultured fibroblasts (WI-38), ovarian carcinoma cells (SK-OV-3), or malignant melanoma cells (SK-MEL-28 and MeWo). In subsequent tests against cultured cell lines, G10 gave positive reactions with 30 of 33 SCC lines but only 4 of 29 non-SCC lines. The non-SCC lines that bound G10 were UM-PAd-1, 2 transitional cell carcinoma lines (T24 and RT4), and 1 melanoma line (SK-MEL-22). When tested against cultures derived from normal skin or mucosa, G10 was reactive with the epitheloid squamous cells but not with the fibroblasts in each culture. The antigen defined by antibody G10 was stable to fixation with Formalin, and its distribution in tissue sections was examined with the use of immunoperoxidase assays. All SCC biopsy specimens examined in this way were reactive with antibody G10. In similar tests against sections of fixed normal tissues, G10 stained the superficial squamous cells of the epidermis and the basal and suprabasal layers of mucosal squamous epithelial cells from the esophagus. All layers of the laryngeal epithelium were positive. Endothelial cells and certain glandular cells were also positive for G10 binding. G10 agglutinated human red blood cells of all blood groups except those from individuals of the Bombay group (Oh) who lack the H blood group determinant. Against defined oligosaccharides, G10 bound strongly only to the monofucosyl H type 2 structure and was slightly cross-reactive with the synthetic difucosyl H type 2 or Y structure. These results are consistent with previous reports of blood group antigen tissue distribution and indicate that the H type 2 determinant is expressed by all or nearly all mucosal squamous cancers. Less frequent expression by cells of other tumor types may correlate with tissue-specific activation of the H gene-specified fucosyltransferase.
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PMID:Monoclonal antibody (G10) to a common antigen of human squamous cell carcinoma: binding of the antibody to the H type 2 blood group determinant. 241 79

We studied the mechanisms of resistance to interferon (IFN) in two human melanoma cell lines, SK-MEL-28/beta cells resistant to human recombinant beta-interferon (ReIFN-beta) and SK-MEL-28/gamma cells resistant to human recombinant gamma-interferon (ReIFN-gamma). SK-MEL-28/beta cells were resistant to both ReIFN-beta and IFN-alpha, but not ReIFN-gamma or natural gamma-interferon (IFN-gamma), and SK-MEL-28/gamma cells were resistant to both ReIFN-gamma and IFN-gamma, but not ReIFN-beta or IFN-alpha. SK-MEL-28/s cells, sensitive to both ReIFN-beta and ReIFN-gamma, had receptors for ReIFN-beta and ReIFN-gamma. Furthermore ReIFN-beta and IFN-alpha shared the common receptors as judged by competition assays, while the receptors for ReIFN-gamma were independent in SK-MEL-28/s cells. The Kd values of binding of both IFNs to SK-MEL-28/beta or SK-MEL-28/gamma cells were essentially equivalent to those to SK-MEL-28/s cells. Both labeled IFNs were internalized rapidly into all cell lines at 37 degrees C. No significant difference in internalization was found between IFN-sensitive and -resistant cells. Each cell line expressed HLA-AB and Mr 97,000 protein antigens, the expressions of which were enhanced by ReIFN-beta and ReIFN-gamma. Partial resistance to the enhancement of both antigens by both IFNs was seen in the resistant cells. Finally ReIFN-gamma, but not ReIFN-beta, induced a Mr 56,000 protein in SK-MEL-28/s cells. This effect of ReIFN-gamma was also detected in SK-MEL-28/beta cells, but not SK-MEL-28/gamma cells. These results provide some information concerning the nature of IFN-resistant cells. The receptors had no significant correlation with the resistance, while the expression of HLA-AB or Mr 97,000 protein antigens or the induction of proteins had some correlation with the resistance.
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PMID:Analysis of receptors, cell surface antigens, and proteins in human melanoma cell lines resistant to human recombinant beta- or gamma-interferon. 243 Jun 91

Serum antibodies from melanoma patient FD were previously shown to detect a unique antigenic specificity (FD) expressed only on the autologous tumor cells (SK-MEL-131) in culture. The FD determinant is carried by a Mr 90,000 glycoprotein (gp90) that binds to concanavalin A but not to lentil lectin or wheat germ agglutinin. After treatment with endo-N-acetylglucosaminidase H, the antigen no longer bound to concanavalin A. These and other properties indicate the gp90 carries mainly high mannose or hybrid N-linked carbohydrate chains. gp90 was partially purified from a detergent-solubilized membrane preparation by chromatography on DEAE-Sepharose, hydroxylapatite, chelating Sepharose, and lectin-agarose columns. Two-dimensional electrophoresis of the final preparation revealed three major components, one of which was identified as the FD antigen since it was specifically removed by precipitation with serum from patient FD. Immunization with the partially purified antigen preparation elicited anti-gp90 antibodies in two of four mice as demonstrated by sequential radioimmunoprecipitation experiments. Absorption experiments demonstrated that the mouse antibodies could, unlike human FD serum, be absorbed by a number of different cell types. Based on these results it is proposed that gp90 in SK-MEL-131 cells has two distinct epitopes, one, unique, detected by autologous FD serum, and another, common epitope or epitopes, detected by the polyclonal mouse sera. The common epitope(s) is present on gp90 in a variety of cells, including allogeneic melanomas and FD-B cells. These findings, which are compared with those on mouse tumor rejection antigens, have clear implications for the understanding of the nature of tumor antigens.
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PMID:Class 1 (unique) tumor antigens of human melanoma: partial purification and characterization of the FD antigen and analysis of a mouse polyclonal antiserum. 244 75

The objective of this study was to establish whether human recombinant tumor necrosis factor (TNF) can significantly stimulate the proliferation of some tumor cells. Treatment with TNF had little or no effect on the growth of human tumor cells and murine NIH/3T3 cells cultured in medium with high serum concentration. Two tumor lines, SK-MEL-109 melanoma and HOS osteosarcoma cells, were adapted to grow in medium supplemented with 0.5% serum. The growth of these SK-MEL-109 cells was inhibited by TNF, but that of the HOS cells was greatly stimulated by TNF in a dose-dependent way. Treatment with 10 ng/ml of TNF resulted in a two-fold increase in the rate of cell division. This effect of TNF was also shown by measuring DNA and protein synthesis. The continuous presence of TNF was not required for its mitogenic activity on HOS cells cultured with 0.5% serum, since treatment for only one day with TNF resulted in prolonged growth stimulation. The failure of TNF to promote division of cells cultured in medium with 10% serum may possibly be explained by the presence of saturating amounts of growth factors in serum. Interferons abolished the mitogenic activity of TNF on HOS cells. Furthermore, TNF did not show synergism with insulin or epidermal growth factor in stimulating growth of these cells. The level of c-myc mRNA was increased five-fold after 30 minutes of treatment with TNF. This shows that TNF is a growth factor for HOS cells and that it induces accumulation of c-myc mRNA.
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PMID:Tumor necrosis factor stimulates proliferation of human osteosarcoma cells and accumulation of c-myc messenger RNA. 245 Aug 80

Antibodies present in the serum of melanoma patient FD detect an antigenic determinant (FD) restricted to the autologous melanoma cell line SK-MEL-131. This cell-surface determinant is carried on a glycoprotein of 90 kDa, designated gp90. Mice were immunized with a partially purified preparation of gp90 derived from SK-MEL-131 clone 1.5, and three murine hybridomas (KF23, KF26, and KF104) secreting monoclonal antibodies (mAbs) detecting this antigen have been generated. Sequential immunoprecipitation experiments demonstrate that the three mAbs and human FD serum react with the same gp90 species. The mAbs, in contrast to FD serum, react with a broad range of cultured cells in assays for cell-surface antigens and immunoprecipitate a gp90 component from radiolabeled extracts of these cells, including autologous FD B cells. We conclude that gp90 from SK-MEL-131 has two types of determinants: restricted (detected by FD serum) and common (detected by the mouse mAbs). gp90 molecules from cell lines other than SK-MEL-131 carry only the common determinant(s). Immunoperoxidase analysis of frozen tissue sections with mAb KF23 demonstrated a restricted gp90 expression in normal tissues (capillary endothelial cells, duct epithelium in sweat glands, breast, and pancreas). Melanomas and sarcomas showed strong gp90 expression, suggesting up-regulation of gp90 synthesis in certain human cancers.
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PMID:Class 1 (unique) tumor antigens of human melanoma: identification of unique and common epitopes on a 90-kDa glycoprotein. 245 81

The oncolytic strain 73-T of Newcastle disease virus (NDV) has been reported to be beneficial in the treatment of cancer patients, but little is known about its mechanism of action. In this study, NDV strain 73-T and a wild-type isolate of NDV were found to be potent inducers of tumor necrosis factor (TNF) production by both human peripheral blood mononuclear cells (PBMCs) and rat splenocytes. Antibody inhibition experiments identified TNF-alpha as the major species of TNF induced by NDV in PBMCs. The effect of recombinant human TNF-alpha (rHuTNF-alpha) on human cancer cells was then examined. Neither rHuTNF-alpha nor supernatants from NDV-stimulated PBMCs were cytotoxic toward the TNF-resistant human malignant melanoma cell line MEL-14. However, when MEL-14 cells were treated with NDV strain 73-T, both rHuTNF-alpha and supernatants from NDV-stimulated PBMCs killed 48% and 55%, respectively, of these tumor cells. Treatment with NDV also conferred TNF susceptibility to the TNF-resistant human malignant melanoma cell line MEL-21 and the human myelogenous leukemia cell line K562. In contrast to its enhanced cytotoxicity toward NDV-treated cancer cells, rHuTNF-alpha had no effect on NDV-treated normal human PBMCs proliferating in response to concanavalin A. These results suggest two important mechanisms for the antineoplastic activity of NDV: (a) induction of TNF-alpha secretion by human PBMCs and (b) enhancement of the sensitivity of neoplastic cells to the cytolytic effects of TNF-alpha.
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PMID:Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity. 245 2

Analysis of antibodies present in the serum of melanoma patient FD has shown that they detect a unique tumor epitope present only on the autologous melanoma cell line SK-MEL-131. Previous results had shown that the unique FD epitope is carried on a common glycoprotein of approximately 90 kD, widely expressed on melanoma and a few other cell types. We now show by sequential radioimmunoprecipitation and partial amino acid sequencing that this common molecule is a previously recognized melanoma antigen, originally identified by mouse mAbs, designated gp95 or p97 (and also known as melanotransferrin). Thus, FD is the first of the class I (unique) melanoma antigens that has been characterized and related to a known cell surface molecule.
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PMID:A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97. 246 31


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