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)

A cDNA clone of murine macrophage inflammatory protein 2 (MIP-2) has been isolated from a library prepared from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the nucleotide sequence determined. This cDNA was used to clone cDNAs for human homologues of MIP-2 from a library prepared from phorbol myristate acetate-treated and LPS-stimulated U937 cells. Two homologues were isolated and sequenced. Human MIP-2 alpha and MIP-2 beta are highly homologous to each other and to a previously isolated gene, human gro/melanoma growth-stimulating activity (MGSA). These three human genes, MIP-2 alpha, MIP-2 beta, and gro/MGSA, constitute a sub-family within the cytokine family represented by platelet factor 4 and interleukin 8.
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PMID:Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. 220 51

The actin cytoskeleton is important for cell structure and motility. A disordered actin architecture has been correlated with a high metastatic potential in melanoma, fibrosarcoma, and colon cancer models. Thyrotropin is known to induce growth and differentiation in cultured thyroid cells, whereas the carcinogenic phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) causes dedifferentiation and malignant transformation in many cell lines. We therefore assessed the effect of thyrotropin and TPA on the actin architecture of FTC-133 human follicular thyroid cancer cells in continuous culture. Staining of filamentous actin with rhodamine phalloidin showed that 1 mU/ml or 30 mU/ml thyrotropin-induced actin polymerization was detectable at 1 hour but more notable at 24 hours. Similarly TPA (0.008 to 10 mumol/L) caused rapid actin fiber disruption and redistribution to the cell periphery. Secondary antibody staining for alpha-actinin, a protein that binds and crosslinks actin, was more prominent after treatment with thyrotropin but decreased after TPA. These findings indicate that the actin cytoskeleton has a dynamic response to trophic factors. Thyrotropin promoted actin polymerization, but TPA caused depolymerization. These effects may correlate with cellular alpha-actinin levels. Actin architecture may therefore reflect the state of differentiation of thyroid tumor cells.
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PMID:Actin architecture of cultured human thyroid cancer cells: predictor of differentiation? 224 45

Five proteins with anticoagulant and antimetastatic activities were isolated from the salivary glands of the Amazon leech, Haementeria ghilianil. These proteins, designated ghilantens, were co-purified on DEAE-cellulose and heparin-agarose, and were purified by microbore C-18 reverse-phase HPLC. Each variant had a similar molecular weight (18,000), amino acid composition, and a blocked amino terminus. Ghilantens caused a dose-dependent prolongation of the prothrombin time of normal human plasma and blocked the factor Xa-mediated hydrolysis of methoxycarbonyl-D-cyclohexylglycyl-glycl-arginine-p-nitro anillide acetate. Ghilantens were quantitatively absorbed to bovine factor Xa-AffiGel-15 and were eluted with 0.1 mol/L benzamidine, an active-site reversible inhibitor of factor Xa. These findings show that ghilantens can form a reversible association with the enzyme. When administered intravenously to mice by tall vein injection, ghilantens potently suppressed lung metastases of B16-F10 melanoma cells. These findings suggest that ghilantens may have therapeutic value in the treatment of metastatic disease.
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PMID:Ghilantens: anticoagulant-antimetastatic proteins from the South American leech, Haementeria ghilianii. 229 60

Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C.
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PMID:Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA. 230 29

Tumor necrosis factor (TNF) elicits a wide variety of responses in target cells by binding to cell surface receptors, but the signal transduced from these receptors in unclear. We examined the role of two different second messenger systems in the regulation of plasminogen activator inhibitor, type 2 (PAI-2) induction by TNF in SK-MEL-109 melanoma cells. Synthesis of PAI-2 and transcription of its mRNA could be induced by a protein kinase C (PKC) activator, phorbol myristate acetate. In addition, induction of PAI-2 synthesis by TNF was blocked by two PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride. The inhibitor of cyclic nucleotide-dependent protein kinases, N-[2-(methylamino)-ethyl]-5-isoquinoline sulfonamide dihydrochloride, was much less effective in decreasing PAI-2 synthesis. Staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride also inhibited both TNF- and phorbol myristate acetate-induced PAI-2 mRNA accumulation. We measured the binding of 3H-labeled phorbol dibutyrate to membrane and cytosol fractions of TNF-treated SK-MEL-109 cells and found a transient redistribution of 3H-labeled phorbol dibutyrate binding from cytosol to membrane fractions in response to TNF. In contrast to the positive regulation by PKC in promoting TNF-induced PAI-2 synthesis cAMP inhibited this response. Pretreatment of cells with agents that raise intracellular cAMP levels completely abolished TNF-induced PAI-2 synthesis. Addition of cAMP-elevating agents during TNF induction could also block PAI-2 synthesis. PAI-2 mRNA accumulation in response to TNF was inhibited, but not completely abolished, by cAMP-elevating agents, suggesting that cAMP also exerted its inhibitory effect at the translation level. The positive regulation of a TNF response by PKC and its negative modulation by cAMP may provide a means for intracellular coordination of signals from interacting extracellular factors in regulating TNF responses in different target cells.
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PMID:Positive and negative regulation of a tumor necrosis factor response in melanoma cells. 232 95

Secreted phosphoprotein I (SPP), also known as 2ar, osteopontin, 44-kDa bone phosphoprotein, bone sialoprotein I, and transformation-related phosphoprotein, is a 41.5-kDa glycosylated phosphoprotein secreted by many mammalian cell lines and expressed in a limited set of tissues. Using a cDNA probe, we found that SPP mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderate-to-high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous-cell carcinomas induced by an initiation-promotion regimen. This contrasts with the transient induction we had previously observed after a single application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In a set of 5 independently isolated T24-H-ras-transfected mouse C3H 10T1/2 cell lines, the levels of SPP mRNA correlated well with ras mRNA levels and with both experimental and spontaneous metastatic ability. SPP mRNA expression was also elevated in a derivative of mouse LTA cells transfected with genomic DNA from B16F1 melanoma cells and selected for increased experimental metastatic ability in the chick embryo. This apparent association of SPP expression with invasion, progression and metastasis, along with the presence of a functional ArgGlyAsp (RGD) cell adhesion site in SPP (osteopontin), leads us to propose that SPP may act as an autocrine adhesion factor for tumor cells.
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PMID:Secreted phosphoprotein mRNA is induced during multi-stage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts. 236 96

Human skin melanocytes and melanocytes cultured in vitro express GM3 ganglioside almost exclusively, whereas malignant melanomas express high levels of both GM3 and GD3. We now show that treatment of cultured melanocytes with tumor necrosis factor-alpha, particularly in the presence of tetradecanoylphorbol-13-acetate, results in a change in morphology from spindle-shaped to epithelioid and greatly enhanced expression of GD3 ganglioside. This effect is specific and no other ganglioside is affected, except that GM3 expression (which is already high) is also increased. In contrast, these agents did not enhance the already high expression of GD3 on melanoma cells. This result provides an example of the plasticity of glycolipid expression in mammalian cells and their susceptibility to the influence of biological agents.
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PMID:Tumor necrosis factor enhances GD3 ganglioside expression in cultured human melanocytes. 238 25

Treatment of the BL6 melanoma cells in vitro with N-methyl-N'-nitronitrosoguanidine dramatically increased their expression of H-2Kb and H-2Db antigens as well as beta 2-microglobulin but not Class 2 major histocompatibility complex antigens. The treated tumor cells also became immunogenic and were rejected in 70% of syngeneic C57BL/6 recipients, whereas these tumor cells produced progressively growing tumors in 100% of irradiated (550 R) or nude mice. In contrast to the effects of N-methyl-N'-nitronitrosoguanidine treatment, no influence of H-2 antigen expression or tumorigenicity was found when BL6 melanoma cells were treated with 5-azacytidine, phorbol myristate acetate, 5-bromodeoxyuridine, theophylline, or 6-thioguanine. H-2 antigen expression and the tumorigenic properties of 48 individual clones derived from BL6T2 melanoma line and 15 clones from the original BL6 melanoma were investigated. No H-2 antigens were found on the cell surface of the parental BL6 clones, whereas all tum- clones from the BL6T2 line expressed high levels of H-2 antigens. Although four of six tested tum+ clones had high levels of H-2b antigen expression similar to that of tum- clones, they were nonimmunogenic. These data indicate that an increase in major histocompatibility complex antigen expression is essential but not sufficient for the immunogenicity of tumor cells. This conclusion was also supported by the results of interferon treatment of BL6 melanoma cells: this induced an increase in the expression of beta 2-microglobulin and Class 1 H-2b antigens but not an increase in their immunogenicity. Detection of tumor-associated transplantation antigens on the melanoma cells also appeared to be dependent on the level of expression of H-2 antigens. Although tum+ clones grew in normal mice, immune mice were able to prevent the growth of tum+ clones with high levels of H-2 antigens. However, immune mice only partially inhibited the growth of the parental BL6 melanoma or tum+ clones which have low expression of H-2 antigens.
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PMID:Increase in H-2 antigen expression and immunogenicity of BL6 melanoma cells treated with N-methyl-N'-nitronitrosoguanidine. 241 92

The DNA 5-methylcytosine content has been analyzed in the human melanoma cell line M21 at several time points after induction of differentiation by a variety of inducers. 5-Aza-2'-deoxycytidine reduces DNA methylation to about 50% of the control level and this demethylation occurs prior to the establishment of the differentiated phenotype. The DNA synthesis inhibitors cytosine arabinoside, aphidicolin, and hydroxyurea exert different effects on DNA methylation in these cells. Cytosine arabinoside induces an early DNA hypermethylation, which is however reversible and drops to the original level after 24 h. Hydroxyurea induces DNA hypermethylation after a lag period of more than 48 h and the DNA polymerase alpha inhibitor aphidicolin has no effect on the DNA methylation level. Treatment of cells with phorbol 12-myristate 13-acetate, another potent inducer of melanoma cell differentiation, does not result in a change of total DNA methylation over a period of 96 h. These results indicate that differentiation of human melanoma cells can be accompanied by variable changes of the DNA methylation pattern. These changes can be neither generally related to the differentiation process itself nor related to the effects of DNA synthesis inhibition on DNA methylation, but may more likely reflect a direct or indirect particular effect of the inducer on the DNA methylation process.
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PMID:Variable DNA methylation changes during differentiation of human melanoma cells. 245 5

Nuclear localization of nerve growth factor (NGF) in HS 294 melanoma cells and SW 707 colorectal carcinoma was determined by indirect immunofluorescence staining and by cell fractionation. NGF receptors were immunoprecipitated from the EcoRI-digested chromatin of HS 294 melanoma cells, of melanocytes proliferating in the presence of 12-O-tetradecanoylphorbol-13-acetate, and of SW 707 colorectal carcinoma cells, using a monoclonal antibody to the Mr 75,000 cell surface NGF receptor. Melanoma cells expressed a receptor species with a molecular weight of 230,000. Proliferating melanocytes expressed a small amount of Mr 230,000 receptor, whereas colorectal carcinoma cells expressed a Mr 35,000 receptor. Scatchard analysis indicated one type of NGF chromatin binding site in HS 294 cells with KD = 241 pM but two types of binding sites in chromatin of SW 707 cells with KD = 333 and 1718 pM, respectively. Both the Mr 230,000 and the 35,000 receptor species were tightly bound to DNase II-sensitive regions, which became DNase II-insensitive after nerve growth factor binding. [125I]NGF was detected in the chromatin in nondegraded form. Chromatin binding of NGF inhibited RNA synthesis and cell proliferation.
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PMID:Nerve growth factor receptors in chromatin of melanoma cells, proliferating melanocytes, and colorectal carcinoma cells in vitro. 246 Dec 54


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