UMLS:C0025202 - FACTA Search

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

Human melanoma cells, but not tumor cells of other histological origin, express a unique membrane-associated glycoprotein, designated ME20-M, and secrete a soluble glycoprotein, designated ME20-S, defined by monoclonal antibody ME20. Here we report the isolation and characterization of a cDNA clone that when transfected into COS cells directs the expression of ME20-M and ME20-S. This cDNA contains an open reading frame which encodes a 661-amino-acid-long precursor that contains a 23-amino-acid signal peptide and a 26-amino-acid transmembrane domain, separated by a hydrophilic region containing 5 potential Asn-linked and 14 predicted Pro-associated, Thr-linked glycosylation sites. The transmembrane domain is followed by a carboxy-terminal 45-amino-acid putative intracellular domain rich in Ser residues. Analysis of ME20-M by amino acid sequencing identified the proteolytic processing site. Signal peptide cleavage occurs at the Thr-24-Lys-25 peptide bond of the precursor and results in the 637-amino-acid ME20-M with a calculated molecular weight of 67,782. ME20-M is derived from a single 3.3- to 3.4-kb mRNA transcript that is expressed at varying levels in melanoma cell lines, correlating with immunofluorescence determination of protein expression. The amino acid sequence of the ME20 antigen deduced from the cDNA differs from the human neonatal melanocyte-specific Pmel 17 gene product by a single amino acid substitution and deletion of 7 amino acid residues, and it is 80% homologous with the bovine retinal pigment RPE1 cDNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning and expression of the gene for the melanoma-associated ME20 antigen. 817 25

A great variety of cells, such as melanoma cells, fibroblasts, platelets, keratinocytes, and epithelial cells, adhere to and migrate on specific regions within the triple-helical domains of types I, III, and IV collagen. The relative importance of collagen primary, secondary, and tertiary structures on these cellular activities has not been ascertained, as no general synthetic methodology exists to allow for the study of peptides incorporating biologically active sequences in triple-helical conformation. We have thus developed a novel, generally applicable solid-phase branching methodology for the synthesis of aligned, triple-helical collagen-model polypeptides (i.e. "mini-collagens"). Three nascent peptide chains are carboxyl-terminally linked through one N alpha-amino and two N epsilon-amino groups of Lys, while repeating Gly-Pro-Hyp triplets induce triple helicity. A homotrimeric triple-helical polypeptide (THP) of 124 amino acids, incorporating residues 1263-1277 of alpha 1 (IV) collagen, was synthesized. Highly metastatic mouse melanoma cells showed a profound preference for adhesion to this THP as compared with a single-stranded peptide (SSP) incorporating the same type IV collagen sequence or a branched peptide containing eight repeats of Gly-Pro-Hyp (designated GPP*). Specifically, 50% cell adhesion occurred at a THP concentration of 1.12 microM, while comparable levels of adhesion required [SSP] = 170 microM or [GPP*] > 100 microM. Melanoma cells also spread on the THP to a greater extent than on the SSP or GPP*. These results are the first direct demonstrations of the significance of triple helicity for cell adhesion to and spreading on a specific collagen sequence and support earlier conclusions of conformational dependency for cell adhesion to and migration on types I and IV collagen. In addition, the melanoma cell THP activities support the concept that tumor cell adhesion and spreading on type IV collagen involves multiple, distinct domains in triple-helical conformation. The triple-helical peptide synthetic protocol developed here will allow eventually for the study of both structure and biological activity of specific, glycosylated collagen sequences in homotrimeric and heterotrimeric forms.
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PMID:Melanoma cell adhesion and spreading activities of a synthetic 124-residue triple-helical "mini-collagen". 831 81

The Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide derived from the laminin B1 chain has been shown to decrease tumor growth and metastasis. Utilizing the multimeric antigen peptide system assembled on a branched lysine core, we synthesized several sizes of multimeric YIGSR, (CH3CO-Tyr-Ile-Gly-Ser-Arg-Gly)16-Lys8-Lys4-Lys2 -Lys-Gly [(Ac-YIGSRG)16 K8K4K2KG] (designated Ac-Y16), (Ac-YIGSRG)8K4K2KG (Ac-Y8), and (Ac-YIGSRG)4K2KG (Ac-Y4), and related peptides, Ac-(YIGSRG)4-NH2 (Ac-Y4L) and Ac-YIGSR-NH2 (Ac-Y1) and evaluated their biological activities in inhibiting tumor growth and metastasis. Coinjection of 0.2 mg/mouse of Ac-Y16 i.v. with B16-F10 mouse melanoma cells inhibited lung colony formation by 97%, whereas 0.2 mg/mouse of Ac-Y1 inhibited by 50%. The larger the peptide (Ac-Y16 > Ac-Y8 > Ac-Y4 > Ac-Y1), the more inhibitory effect there was on lung metastasis. Ac-Y16 also inhibited the growth of s.c.-injected B16-F10 tumors. These data demonstrate that the multimeric YIGSR peptides strongly enhanced the activity of YIGSR in inhibiting tumor growth and metastasis and suggest that these compounds are potentially useful for clinical applications.
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PMID:Multimeric forms of Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide enhance the inhibition of tumor growth and metastasis. 833 46

A beta-lactosyl residue was linked to the amino groups of L-lysyl-L-lysine through spacer arms of three different lengths (C2, C4, and C9) to give trivalent beta-lactosyl clusters in order to increase the inhibitory activity of the beta-lactosyl group against tumor cell colonization. Thus, O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-2,3, 6-tri-O-acetyl-glucopyranosyl trichloroacetimidate was treated with methyl or benzyl hydroxyethanoate, methyl or benzyl 4-hydroxybutanoate, and methyl 9-hydroxynonanoate, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate to give the corresponding beta-lactosides. These were coupled to L-lysyl-L-lysine, after conversion to the N-hydroxysuccinimide esters, to yield the corresponding trivalent beta-lactosyl-L-lysyl-L-lysine conjugates in good yields. The beta-lactosyl group with a C4 spacer arm was also coupled similarly to poly(L-lysine) (M(r) 3800) to form a polyvalent beta-lactosyl cluster. Coinjection of the trivalent (with C2 and C4 spacer arms) and polyvalent beta-lactosyl clusters with the highly metastatic B16 murine melanoma cells inhibited the formation of lung colonies in C57/BL mice, whereas the trivalent cluster with a C9 spacer arm displayed no activity.
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PMID:Synthesis of multivalent beta-lactosyl clusters as potential tumor metastasis inhibitors. 837 21

Antiserum was produced in rabbits against the polyamine spermidine (Spd) conjugated to bovine serum albumin (BSA). The reactivity of the serum to Spd and a variety of structurally related compounds was quantified by a new immunocytochemical model system incorporating an enzyme-linked immunosorbent assay (ELISA) binding test. This is based on the principle of coupling these compounds to the wells of microtiter plate activated with poly-L-lysine and glutaraldehyde and incubating the wells by the indirect immunoperoxidase method. The antiserum showed a 25% cross reaction with spermine (Spm), putrescine (Put), and cadaverine (Cad), and a 1% cross reaction with 1,3-diaminopropane (Dap), but no cross reaction with monoacetyl polyamines and amino acids. The antibody binding was inhibited most effectively by absorption of the antiserum with N1-acetylspermidine and Spd in the ELISA inhibition test. Also, immunoblot analysis of the antiserum with nitrocellulose paper gave completely identical results to the ELISA binding tests. Spd-like immunoreactivities in human melanoma BD and neuroblastoma IMR 32 cell lines are presented as examples of the staining pattern obtained with the antiserum. Absorption of the serum with N1-acetylspermidine and Spd was demonstrated to abolish the immunostaining reaction. The immunohistochemical model is simple: amines and amino acids are bound in the same way as in aldehyde-fixed tissues and, in comparison to immunoblot analysis, the immunoreactivity can be more easily and accurately quantified by assay with the antibody. The model should prove useful in assessing the specificity of other antisera.
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PMID:A new enzyme-linked immunosorbent assay (ELISA) for studying immunocytochemical procedures using an antiserum produced against spermidine as a model. 840 72

Laminin is an important promoter of cell-matrix interactions. A number of active laminin domains have been defined by use of synthetic peptides. The Tyr-Ile-Gly-Ser-Arg (YIGSR) sequence on the B1 chain in laminin can decrease tumor growth and metastasis, whereas another sequence containing Ser-Ile-Lys-Val-Ala-Val (SIKVAV) on the A chain can increase tumor growth and metastasis. Here, we selected B16-F10 melanoma cells by adherence or nonadherence to either YIGSR- or SIKVAV-coated dishes and established 3 B16-F10 variants: YIGSR-adherent cells (Y+), YIGSR-nonadherent cells (Y-), and SIKVAV-nonadherent cells (S-). SIKVAV-adherent cells were not selected because most of F10 cells attached to the SIKVAV-coated dish. These cell lines proliferated at the same rate as the parent F10 cells and attached equally to laminin, collagen IV, and fibronectin. Y+ cells produced rapidly growing tumors after s.c. injection and twice as many lung colonies as the parental F10 cells after i.v. injection. In contrast, Y- cells produced more slowly growing tumors after s.c. injection and produced one-third of the lung colonies relative to the parent cells after i.v. injection. S- cells produced slowly growing tumors after s.c. injection and yielded similar numbers but smaller colonies in the lung than the parental B16-F10 cells after i.v. injection. These data suggest that interactions of melanoma cells with the YIGSR site on laminin are probably important for both colony formation in a target organ (lung) and subsequent tumor growth, while the SIKVAV-containing site on laminin may be more important for tumor growth.
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PMID:Melanoma cells selected for adhesion to laminin peptides have different malignant properties. 841 34

Laminin is a large multidomain protein with diverse biological activities. We previously demonstrated that intact laminin as well as an A chain synthetic peptide (LamA2091-2108) stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation. Here we report that LamA2091-2108 increases t-PA production by the highly metastatic murine melanoma cell line B16F10, with no effect on the parental B16F1 line, which has a low metastatic capacity. Incubation of plasminogen with B16F10-conditioned medium results in direct activation of the zymogen to plasmin. Furthermore, following incubation of B16F10 cells with plasminogen, plasmin is eluted from the cell surface, suggesting that these cells contain binding sites for plasminogen/plasmin in close proximity to t-PA binding sites. Quantitation of t-PA activity using the synthetic substrate Val-Leu-Lys-p-nitroanilide indicates a minimal 10-fold increase in t-PA in the conditioned medium of B16F10 cells grown in the presence of LamA2091-2108, with no increased t-PA activity observed in B16F1-conditioned medium. Similar results were obtained in immunocapture experiments which are specific for t-PA antigen. In addition, B16F10 melanoma-associated t-PA catalyzes the plasminogen-dependent hydrolysis of laminin. Together these data suggest that degradation of basement membrane proteins by metastatic melanoma cells may release fragments (such as LamA2091-2108) which stimulate both the production and activity of metastasis-associated proteinases such as t-PA, providing a mechanism for augmentation of the metastatic capacity of B16F10 melanoma cells.
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PMID:Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain. 848 2

We have shown (Bizik et al., Cell Regul 1:895-905, 1990) that tPA can activate plasminogen on the surface of human melanoma cells in the presence of alpha 2-macroglobulin (alpha 2M) secretion. In the present study, we investigated the binding of tPA on the surface of Bowes melanoma cells, selected since they lacked production of PAI-1 and alpha 2M. Elution of tPA from the cell layers indicated that polylysine (5 micrograms/ml) and tranexamic acid (10 mM), an analog of lysine, were the most efficient agents for disrupting the interaction between tPA and cell surface component(s). Using a panel of monoclonal antibodies against individual domains of tPA revealed that an antibody directed to the kringle-2 domain of tPA interfered most significantly with cell-surface plasmin generation. As tPA is a glycoprotein, interactions between the tPA sugar moieties and cell surface were also tested by the use of a series of monosaccharides. N-acetyl-D-glucosamine (100 mM) was the most potent sugar to release tPA from melanoma cells, but the results indicated that the oligosaccharides of tPA play only a supportive role in the binding of tPA to the cell surface. Quantitative comparison of the cell surface localized tPA, which was eluted by tranexamic acid, with the total cellular tPA showed that cell surface bound tPA could represent up to 10%. We conclude that tPA interacts with the melanoma cell surface in a similar manner as has been described for binding of tPA to fibrin and to the putative endothelial cell surface receptor.
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PMID:Binding of tissue-type plasminogen activator to human melanoma cells. 850 Nov 35

The biodistribution has been studied in mice with subcutaneously transplanted solid tumours (mammary carcinoma and melanoma) of synthetic branched-chain polypeptides based on poly(L-lysine). The polypeptides were a poly(L-lysine) backbone with side-chains of three DL-alanine residues (AK, which is polycationic), AK with additional glutamic acid residues at the end of the side-chains (EAK, which is amphoteric) and EAK in which the terminal glutamic acid amino groups had been acetylated (AcEAK, which is polyanionic) or succinylated (SucEAK, which is highly polyanionic). Polypeptides were labelled with 125I by reaction with Bolton and Hunter reagent, or with 111In by chelation to diethylenetriaminepentaacetic acid previously conjugated to them. As controls, natural plasma proteins (immunoglobulin G, albumin and transferrin) were similarly labelled. Over a study period of up to 7 days, even with the polypeptides showing most prolonged blood survival (EAK and AcEAK) there was no particular uptake or retention in tumour tissue, over and above what was seen with control plasma proteins and/or in normal tissues. Overall these findings suggest that any enhanced permeability and retention in tumour tissue, reported by other workers with other synthetic macromolecules, operates poorly with the present polypeptides and/or tumours. Specific tumour targeting, for example with monoclonal antibodies, would seem a better option than non-specific accumulation of macromolecules.
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PMID:Biodistribution in tumour-bearing mice of polycationic, amphoteric and polyanionic branched polypeptides with a poly(L-lysine) backbone labelled with 125I and 111In: tumour accumulation less than that of labelled serum proteins. 854 92

Variation in the degree of prolonged (residual) biological activity of the melanotropin peptides alpha-MSH (alpha-melanocyte-stimulating hormone, Ac-Ser-Tyr-Met-Glu- His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and the superpotent analogues [Nle4,DPhe7]alpha-MSH (MT-I) and Ac-[Nle4,Asp5,DPhe7,Lys10]alpha-MSH(4-10-NH2 (MT-II) has stimulated considerable interest regarding this biological phenomena. We have examined the differences in their relative dissociation rates from the melanocortin receptor, hMC1R, to try and correlate peptide dissociation rates with the observations of prolonged biological activity. Interestingly, these studies revealed that alpha-MSH remained 25% bound, MT-I 65% bound, and MT-II 86% bound 6 h after the ligand had been removed from the assay medium. The relative dissociation rate of MT-II was 4 times slower than that for alpha-MSH and 2 times slower than that for MT-I, which was 2 times slower than that for alpha-MSH. These data suggest that slow dissociation kinetics (hours) may contribute to the prolonged biological activities observed for both MT-I and MT-II peptides in vitro and in vivo. The prolonged binding, biological activities, and enzymatic stability of MT-I and MT-II make them putative candidates for clinical uses such as external scintigraphy for the localization of tumors (i.e., melanoma).
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PMID:Characterizations of the unusual dissociation properties of melanotropin peptides from the melanocortin receptor, hMC1R. 855 11

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