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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of the humoral immune response of patients with melanoma has identified a small group of individuals with antibody to cell surface antigens that are restricted to autologous melanoma cells. These antigens, referred to as Class I or unique tumor antigens, are demonstrated by reactions between serum and cultured melanoma cells from the same patient and absorption tests with autologous and allogeneic normal and malignant cells to determine antibody specificity. Five Class 1 melanoma antigens have been defined to date, but insight into the nature of these antigens has been limited because antibodies identifying these antigens lacked detectable immunoprecipitating activity. We have now defined a Class 1 melanoma antigen (designated FD) that is immunoprecipitated by autologous antibody. FD antigen is identified by an IgG antibody present in the sera of patient FD, and peak titers of this antibody in tests with cultured autologous melanoma cells are in the range of 1:2048. By absorption tests, FD antigen could not be detected on any other cell type, including 33 allogeneic melanomas. Prolonged culture of FD melanoma cells resulted in decreased expression of FD antigen, but sublines could be obtained with stable antigen expression. FD antigen is trypsin and heat sensitive, neuraminidase resistant, and is shed in the culture medium. Immunoprecipitation of 125I-labeled cell membrane preparations revealed a 90,000 dalton component of pI 5.5. Serum immunoprecipitating activity could be absorbed by autologous melanoma cells but not by autologous B cells or allogeneic cell lines. A component of the same molecular mass could be precipitated from lysates of cells metabolically labeled with [3H]mannose. The membrane form of the FD antigen binds strongly to Con A-Sepharose and can be eluted with methyl-alpha-D-mannoside. The identification of a precipitating Class I antigenic system of melanoma facilitates efforts to generate monoclonal antibodies to this tumor antigen and to clone its coding sequence.
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PMID:Class 1 (unique) tumor antigens of human melanoma. Identification of a 90,000 dalton cell surface glycoprotein by autologous antibody. 623 65

Because tumor-induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor-induced platelet aggregation as well as the effect of various anti-platelets agents. Two mechanisms for tumor-induced platelets aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo-lipo-protein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phospholipid component of the tumor membrane. We now report a new mechanism of tumor-induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen-induced metastatic murine colon carcinoma, CT26. These tumors do not require cell-surface sialic acid or serum complement as does the first mechanism. They do not require cell-surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin-sensitive surface protein for activity. The ability of the thrombin-generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin-competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacyclin, 6-keto-PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor-induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti-platelet pharmacologic agents. Sensitivity to anti-platelet agents correlates with the mechanism by which tumor cells aggregate platelets.
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PMID:A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases. 629 77

The binding of 125I-labeled nerve growth factor (NGF) to human melanoma cell (A875) membranes, detergent-soluble membrane extracts, and membrane extracts reconstituted into phospholipid vesicles was significantly increased when binding was carried out in the presence of wheat germ agglutinin (WGA). In the absence of WGA, all 125I-NGF binding was rapidly eliminated by trypsin treatment or rapidly dissociated in the presence of a high concentration of unlabeled NGF. However, in the presence of WGA, up to 75% of 125I-NGF bound was resistant to trypsin digestion and was only slowly dissociated by a high concentration of unlabeled NGF. The effects of WGA can be blocked or reversed by N-acetylglucosamine. Both WGA and NGF rapidly associate with soluble extracts and reconstituted vesicles and, at the concentrations used here, reach binding equilibrium within 2 min. The conversion to slowly dissociating, trypsin-resistant binding, however, was not complete for at least 10 min. Both WGA and NGF are required for maximum accumulation of trypsin-resistant, slowly dissociating binding. The order of addition of NGF and WGA has no effect on the rate of conversion of NGF-receptor, and the conversion occurs after both NGF and WGA are present. The amount of conversion is dependent on the incubation temperature, and significantly greater conversion occurs at 37 than at 0 degrees C. The generation of the trypsin-resistant, slowly dissociating state of NGF-receptor is consistent with a time- and temperature-dependent conformational change in NGF-receptor which occurs after interaction of both NGF and WGA with the receptor or closely associated structures.
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PMID:Change in state of nerve growth factor receptor. Modulation of receptor affinity by wheat germ agglutinin. 630 53

PC12 is a nerve growth factor (NGF) responsive cell line which exhibits two classes of NGF receptors distinguishable by different kinetic rate constants, sensitivity to trypsin and resistance to Triton detergent solubilization. Whereas incubation of PC12 cells with wheat germ agglutinin (WGA) prior to addition of 125I-NGF inhibits binding of NGF to both classes of receptors, treatment with WGA subsequent to incubation with NGF does not inhibit NGF binding but causes the class of NGF receptors which exhibit rapid or "Fast" dissociation kinetics prior to lectin treatment to be converted to the form which exhibits "Slow" dissociation kinetics. This WGA-mediated receptor conversion is lectin specific, blocked by N-acetyl-D-glucosamine, occurs at similar rates at 4 and 37 degrees C, and is not impaired by a metabolic poison. NGF receptors converted by WGA, like pre-existing Slow receptors, are resistant to trypsinization and remain associated to Triton X-100 extracted "cytoskeletons." Very similar results were obtained for NGF receptors on a human melanoma cell line A875. These results suggest that Fast and Slow receptors are two interconvertible forms of a single protein, rather than distinct proteins. The significance of the generality of these properties for NGF receptors from diverse species and cell types is discussed.
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PMID:Modification of nerve growth factor receptor properties by wheat germ agglutinin. 631 20

Rat PC12 pheochromocytoma and human A875 melanoma cells express nerve growth factor (NGF) receptors on their surfaces. Covalent crosslinking of bound 125I-NGF to PC12 or A875 intact cells or plasma membrane-enriched fractions resulted in labelling of a peptide doublet at Mr = 110,000 and a single labelled peptide at Mr = 200,000 for each of the cell and membrane preparations. However, a difference between equilibrium binding properties of NGF-receptor on PC12 and A875 cells was observed. PC12 cells exhibited biphasic binding properties with two apparent binding sites: KD = 5.2 nM sites and KD = 0.3 nM sites. The high-affinity PC12 binding sites were trypsin resistant, and 125I-NGF dissociated slowly from them. A875 cells exhibited sites with homogeneous properties (KD = 1.0 nM), all binding sites were trypsin sensitive, and 125I-NGF dissociated rapidly in the presence of unlabelled NGF. Membrane-enriched fractions from either cell type contained binding sites with a uniform low affinity (KD = 3 nM) that were trypsin sensitive, and 125I-NGF rapidly dissociated from them. Sixty to 80 percent of binding sites in membranes could be converted to the high-affinity, trypsin-resistant state by addition of wheat germ agglutinin (WGA). The loss of high-affinity, trypsin-resistant sites from PC12 cells during preparation of plasma membrane fractions does not appear to be the result of selective isolation of low-affinity sites or proteolytic degradation since there is a loss of 125I-NGF binding immediately after cell lysis which is not blocked by protease inhibitors. Also, high-affinity, trypsin-resistant binding sites are not found associated with other cell fractions. The differences between receptor properties on PC12 cells and on A875 cells apparently are the result of differences in the respective intracellular environments. Thus, significant structural homology exists between receptors on A875 and PC12 cells. Cell components other than the binding unit of the NGF receptor may be responsible for the different properties of receptor.
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PMID:A comparison of binding properties and structure of NGF receptor on PC12 pheochromocytoma and A875 melanoma cells. 632 98

Immunofluorescence was used to examine antibodies to cellular antigens in the sera of patients with malignant melanoma. Sera from 60 melanoma patients and from 33 control individuals (13 normal subjects and 20 disease controls) were studied. Ninety % of the melanoma sera were found to have antinuclear antibodies when epithelial cell lines or melanoma lines were used as substrates for their detection, compared to 18% in the control group. Antinucleolar antibodies and anticytoplasmic antibodies were present in 32 and 17%, respectively, in malignant melanoma but none in the controls. Antinuclear and antinucleolar antibodies could be classified into different types according to different patterns of staining and susceptibility of antigens to digestion with DNase, RNase, and trypsin. Certain types of antibodies, such as those showing granular nuclear staining, appeared to be associated with less advanced stages of malignant melanoma, whereas those showing nucleolar and large speckled nuclear staining were associated with more advanced stages of the disease.
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PMID:Antinuclear, antinucleolar, and anticytoplasmic antibodies in patients with malignant melanoma. 633 6

Serum-free medium conditioned by activated cells of the acute monocytic leukemia line, THP-1, was examined for growth-inhibitory activity with several established human cell lines. Free-floating clusters of THP-1 cells were activated into adherent nonproliferating cells by a 24-hr exposure to 10(-7) M mezerein in Roswell Park Memorial Institute 1640 medium containing 1% fetal bovine serum. Adherent cells were incubated for an additional 24 hr in serum-free medium containing insulin (5 micrograms/ml). Dose-response studies revealed that a cervical carcinoma (HeLa), a melanoma (A375Ag5), and several mammary carcinoma cell lines (MCF-7, BT474, MDA-MB415, and T47D) were growth inhibited by this conditioned medium. We concluded, from the results of thymidine release assays and from experiments on reversibility, that inhibition was a cytostatic and not a cytolytic response. In contrast, THP-1 conditioned medium stimulated the growth of two mammary lines (ZR75-1 and HBL-100), a lung type II carcinoma (549), and a colon adenocarcinoma (SW48). Preliminary characterization showed that the inhibitory activity was stable to acid and urea treatment but was destroyed by trypsin and sodium dodecyl sulfate. Molecular sieve chromatography of acetic acid-extracted material separated the inhibitory and stimulatory components.
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PMID:Production of growth-inhibitory activity in serum-free medium by human monocytic leukemia cells. 634 88

The stability of expression of a membrane antigen on human FME melanoma cells was investigated by means of flow cytometric cell sorting and analysis. The melanoma-associated 250 kd antigen was strongly expressed on all cells, as recognized by binding of the monoclonal antibody 9.2.27. By flow cytometric cell sorting, cells of high and low antigen expression were isolated, and the difference in antigen expression between the two populations was examined as a function of time in culture. Immediately after sorting, the median fluorescence intensities of the two populations differed by a factor of 2.7. After the first few days in culture, much of the range in antigen expression of the parent population was regenerated. However, a lasting difference in antigen expression was established, corresponding to 50% higher density of antigen on the cells sorted for high fluorescence intensity, compared to those sorted for low intensity. After trypsin treatment, which removed the antigen from the cell surface, normal antigen expression was regained after 2-3 days in culture, with the same difference between the two populations as before the trypsin treatment. The stability of the established difference in antigen expression between the two sorted subpopulations indicates that expression of this antigen is a precisely controlled, heritable characteristic of the FME melanoma cells.
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PMID:Stable quantitative differences of antigen expression in human melanoma cells isolated by flow cytometric cell sorting. 638

Growth of highly invasive B16 melanoma BL6 cells with bromodeoxyuridine (BUdR) decreases in vitro cell detachment and modulates extrapulmonary growth in vivo. We now show: (1) The presence of an 80 kd glycoprotein in the Triton-insoluble matrix of control BL6 cells but not in the corresponding fractions from BUdR-treated BL6 cells and poorly metastatic F1r cells. (2) The matrix fractions from the two last mentioned cells reveal Triton-insoluble glycoproteins of about 55-58 kd. (3) Mild trypsin treatment of intact cells before matrix preparation leads to the preferential disappearance of the 80 kd component from control BL6 matrix, suggesting its extracellular localization. (4) Prevention of Triton-mediated BL6 matrix detachment by zinc chloride pretreatment, and analysis of different BL6 clones with significant metastatic behavior, also revealed the presence of 80-90 kd matrix-associated glycoproteins in control but not in corresponding BUdR-grown cultures. Since BUdR decreases cell detachment, extrapulmonary metastasis and the levels of the 80-90 kd Triton-insoluble glycoprotein species in metastatic B16 melanoma, and this matrix component is also decreased in poorly metastatic F1r cells, we propose an involvement of this glycoconjugate in tumor cell detachment and metastatic behavior.
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PMID:Relationship of a novel extracellular matrix glycoprotein to cell detachment in highly metastatic B16 melanoma: modulating effect of bromodeoxyuridine. 648 Jan 59

Seeds of the legume Erythrina latissima contain a 20,000-dalton, single-chain protein that has been shown to inhibit the amidolytic activity of trypsin and tissue plasminogen activator. It had no comparable effect on urokinase. IC50 values of 1.1 X 10(-7) M for tissue plasminogen activator and 6.9 X 10(-10) M for trypsin were determined by titration. When coupled to agarose, the Erythrina inhibitor provided an effective reagent for affinity purification of tissue plasminogen activator from melanoma cell-conditioned tissue culture medium. Using this as a single-step procedure, 270-fold purified enzyme was reproducibly obtained with yields of 90% or greater. Both one- and two-chain forms of tissue plasminogen activator were purified. The enzyme migrated, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as a predominant 72,000-dalton doublet with lesser amounts of immunochemically similar, 115,000- and 68,000-dalton components.
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PMID:Purification of human tissue plasminogen activator with Erythrina trypsin inhibitor. 654 Dec 21


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