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

Membranes from a B16 murine melanoma clone of high experimental metastatic capacity show increased amounts of pertussis toxin (PT) substrate when compared to a low metastatic counterpart. Using specific antibodies, we identified Gi2 as the PT-sensitive G-protein uniquely abundant in highly metastatic cells. ADP ribosylation of a G-protein alpha subunit by PT decreased both the migration of tumor cells through Matrigel (Collaborative Research, Bedford, MA) and the fibronectin-, laminin-, and collagen type IV-mediated motility of a high metastatic clone. Treatment of cells from a low metastatic clone with PT did not alter either the relatively low invasive capacity or lower motility of these cells. While cholera toxin treatment of cells resulted in decreased invasion and motility of both high and low metastatic clones, there were significant qualitative and quantitative differences, when compared to the PT effects, which indicated that the two toxins were acting on different second messenger systems. PT treatment of B16 clones of high or low experimental metastatic capacity does not result in any alteration in cellular cyclic AMP accumulation suggesting that the PT substrate is not linked with the adenylyl cyclase enzyme complex. The data suggest that a PT-sensitive G-protein, possibly Gi2, regulates second messenger pathways that contribute to the metastatic capacity of B16 melanoma cells.
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PMID:G-protein involvement in matrix-mediated motility and invasion of high and low experimental metastatic B16 melanoma clones. 247 50

The presence of both laminin and type IV collagen was sought at the dermo-epidermal junction and in the dermis adjacent to benign melanocytic naevi of the junctional, compound, and intradermal types; dysplastic naevi; and both primary and secondary melanoma. In all, 154 lesions were studied, using antibodies to laminin and type IV collagen and an indirect immunoperoxidase technique. The staining patterns seen with the two antibodies were virtually identical, although that of laminin was generally fainter. Breaks in and thinning of the normally continuous line of type IV collagen and laminin at the dermo-epidermal junction were seen in association with the junctional activity of benign naevi, and in malignant melanomas in association with invasive tumour cells. Both benign and malignant cells of the melanocyte series showed relatively light pericellular staining around individual cells and clusters of cells in the papillary dermis. This staining pattern was much stronger in the deeper reticular dermis. It is concluded that the pattern of staining of these two antibodies and in particular the presence of breaks in type IV collagen and laminin at the dermo-epidermal junction are not specific for either benign or malignant melanocytic lesions and cannot be used as a diagnostic marker of invasive malignancy.
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PMID:Type IV collagen and laminin staining patterns in benign and malignant cutaneous lesions. 247 64

Plasminogen activators (PAs) convert plasminogen to plasmin by the cleavage of the Arg-Val bond. There are two distinct types of PA, tissue type (t-PA) released from the endothelial cells of the blood vessels and urinary type (u-PA) released from urinary tubules. u-PA was found to be released from activated macrophages and virally transformed cells. t-PA was also found to be released from breast cancer cells induced by carcinogens or melanoma cells. In structure, t-PA has a finger domain homologous to fibrin-binding domain of fibronectin and a growth factor domain homologous to the epidermal growth factor. u-PA has no finger domain but has a growth factor domain. It is proposed that PA may be important in tumor growth due to the stimulation of tumor cells through binding of growth factor domain to its receptor of tumor cells. Another hypothesis is that PA may activate procollagenase to collagenase, which digests collagen to facilitate tumor growth. We have measured the concentrations of t-PA and u-PA in plasma, urine and tumor tissues of patients with cancer of the digestive tract and patients with uterine or ovarian tumors. The results indicate that the concentrations of u-PA increased in urine, plasma and cancer tissues of patients with cancer of the digestive tracts whereas no increase was observed in t-PA levels. On the other hand, the concentration of t-PA increased mostly in plasma of patients with uterine and ovarian cancers, but t-PA levels in tissues did not increase in patients with uterine and ovarian cancer.
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PMID:Plasminogen activators: possible roles in cell proliferation. 250 84

We have identified a protein(s) on the surface of hepatocytes that binds to the core protein of the heparan sulfate proteoglycan of basement membranes. These cells attached and spread on substrates prepared from the basement membrane heparan sulfate proteoglycan (HSPG) and its core protein (HSPG-core). Three proteins (Mr = 38,000, 36,000, and 26,000) were found to bind to a HSPG-core affinity column using extracts of iodinated hepatocytes, whereas proteins extracted from isolated membranes contained primarily the larger protein (Mr = 38,000). Similar results were obtained using a solid phase binding technique using labeled HSPG-core. Binding of HSPG-core to the protein (Mr = 38,000) was not altered by the presence of an excess of heparin, heparan sulfate, fibronectin, laminin, or collagen IV but was reduced by unlabeled HSPG-core. Similar studies showed that the binding protein (Mr = 3,0000) was present in extracts from the membranes of Engelbreth-Holm-Swarm tumor cells, Madin-Darby canine kidney cells, COS cells, melanoma cells, and rat kidney epithelial cells but not in fibroblasts. The protein was found in increased amounts in 3T3 cells treated with retinoic acid. These observations suggest that a variety of cells that contact basement membrane contain the proteoglycan-binding protein.
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PMID:Identification of a cell surface-binding protein for the core protein of the basement membrane proteoglycan. 252 26

This study sought to determine whether human melanoma cells express integrin-related receptors that mediate their adhesion to laminin. We found that antibodies against the integrin beta 1 chain blocked cell attachment to laminin-coated surfaces. Furthermore, immunofluorescence staining demonstrated beta 1 complexes in vinculin-positive focal adhesion plaques on the basal surface of cells attached to laminin substrates. Chromatography of detergent extracts of 125I-surface-labeled cells on laminin-Sepharose columns recovered two major laminin-binding proteins (100 and 130 kDa, reduced) that bound with high affinity to the columns and were eluted with EDTA. Both proteins were specifically immunoprecipitated from column fractions with monoclonal and polyclonal antibodies to the integrin beta 1 subunit, indicating that they form a noncovalent heterodimer complex. The alpha-like subunit is composed of a 30-kDa light chain that is joined by a disulfide bond to the 100-kDa heavy chain. This complex was not recovered from columns of fibronectin- or collagen type I- or IV-Sepharose. Laminin-binding by the alpha beta 1 complex was independent of Arg-Gly-Asp or Tyr-Ile-Gly-Ser-Arg-like sequences, but required the presence of divalent cations. The 100-kDa alpha-like subunit was electrophoretically and immunochemically distinct from the other known alpha subunits, alpha 1-alpha 6. The results indicate that human melanoma cells express a novel laminin-specific integrin beta 1 complex which may mediate the cells' interactions with this ligand.
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PMID:Human melanoma cells express a novel integrin receptor for laminin. 252 55

Incubating B16 melanoma cells with an inhibitor of glucosylceramide (GlcCer) synthetase, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP), led to a considerable decrease in the levels of GlcCer and lactosylceramide (LacCer). The content of ganglioside GM3 was little affected, but the ability to bind a monoclonal antibody against the ganglioside (M2590) was greatly reduced, suggesting that the reduction in the simple glycolipids led to encryption of the membrane antigen. This interpretation is supported by the observation that permeabilization of the treated cells with Triton X-100 restored immunological reactivity. Specificity of the PDMP effect was shown by its lack of effect on the reactivity of two other surface antigens to anti-melanoma monoclonal antibodies M562 and M622, and of the major histocompatibility antigens to anti-H-2KbDb monoclonal antibody. The ability of the treated cells to attach to laminin or type IV collagen was lost but that to fibronectin was not. The effects of the enzyme inhibitor were counteracted by including GlcCer in the culture medium. This indicates that the lipid was absorbed by the cells and utilized like endogenously-formed GlcCer. Cells preattached to laminin or collagen could be induced to round up by addition of inhibitor. In contrast, L-threo-PDMP (which does not block the synthesis of GlcCer) had no effect on the immunologic reactivity of GM3 or the adhesion properties of the cells. However, it did produce considerable accumulation of LacCer. These data suggest that the simple glycolipid, GlcCer, is an essential factor for antigenic expression of the more complex glycolipids on cell surfaces and that there is a close association and interaction between glycolipids and adhesive receptors on the cell surface.
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PMID:Effects of D-threo-PDMP, an inhibitor of glucosylceramide synthetase, on expression of cell surface glycolipid antigen and binding to adhesive proteins by B16 melanoma cells. 253 51

We have shown that a syngenic monoclonal antibody, M2590, established after immunization of C57BL/6 mice with B16 melanoma cells, recognized GM3 (NeuAc) ganglioside. Although GM3 is widely distributed among various normal cells and tissues, the antibody did not react with them. However, it reacted exclusively with melanoma cells from mouse, hamster and human. Preliminary experiments suggested that proteins and lipids as well as GM3 density on B16 cells are involved in the reactivity of GM3 with the antibody. Then, we investigated the biological function of the melanoma antigen, which was secreted from B16 cells into the culture medium. This soluble antigen was shown to suppress the positive immune responses by inhibiting CTL activity in the effector phase and by induction of specific suppressor T cells (Ts) that block CTL generation in the induction phase. Liposomes containing GM3 (NeuAc) but not GM3 (NeuGc) can effectively induce the melanoma specific Ts as did the soluble antigen. The results indicated the tumor cells can escape from host-immune system by stimulating the repertoire of Ts for self-antigen, GM3. To understand the biological role of GM3, we have established mutant clones of no-expressor of GM3 recognized by M2590. The clones were found to have lower attachment to laminin and type IV collagen and poor ability of lung metastasis.
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PMID:[GM3 ganglioside as melanoma specific antigen and its biological function]. 253 60

During invasion and metastasis, tumor cells use a variety of surface adhesion receptors to attach to and invade basement membranes and interstitial stroma. We examined the role of the cell surface integrin-like complex in the attachment of the invasive murine B16-BL6 melanoma cell line to basement membrane. Polyclonal antibodies prepared against integrin-related complexes isolated from hamster BHK cells (anti-ECMR) or mouse erythroleukemia cells (anti-mouse FnR) inhibited the attachment of B16 cells to complex basement membrane matrices and to substrates coated with purified extracellular matrix components (fibronectin, laminin, and type IV collagen). The expression of integrin-like receptors on the surface of B16 cells was confirmed by selective immunoprecipitation of radiolabeled and solubilized membrane proteins with the antibodies. Both antibodies also reacted with an integrin-related fibronectin-binding receptor complex purified by ligand affinity chromatography on fibronectin-Sepharose columns. The anti-integrin antibodies failed to react with the Mr 68,000 laminin-binding protein, suggesting that their inhibition of cell attachment to laminin and complex basement membrane was not due to contaminating antibodies against the Mr 68,000 laminin receptor. The results indicate that the integrin receptor complexes on B16-BL6 cells either interact directly with a diverse set of extracellular-matrix-associated components or somehow modulate the activity and function of other receptors. Thus integrins may have an important role in tumor cell invasion of tissue barriers.
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PMID:Melanoma cell adhesion to basement membrane mediated by integrin-related complexes. 253 59

Integrin receptors may mediate the adhesion of cells to a number of extracellular matrix components. We found that the attachment of human melanoma cells to collagen types I and IV was blocked by antibodies to the integrin beta 1 subunit but not by peptides containing the Arg-Gly-Asp sequence. Ligand affinity chromatography was used to search for integrin-related receptors which mediate adhesion to native collagens. Detergent extracts of surface 125I-iodinated melanoma cells were chromatographed on type I or IV collagen-Sepharose columns. Bound material was eluted and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. EDTA, but not Arg-Gly-Asp peptides, eluted a mixture of two integrin-related heterodimeric complexes. Each complex contained the integrin beta 1 chain with Mr of 110,000 and a distinct alpha chain with Mr of either 200,000 or 150,000. Immunoprecipitation with specific monoclonal antibodies identified the complexes as very late activation antigen (VLA)-1 (alpha 1 beta 1) and VLA-2 (alpha 2 beta 1), respectively. The binding of these receptors to collagen appeared to be specific because they failed to be retained on fibronectin- or laminin-Sepharose columns. Immunofluorescent staining of cells on collagen substrates with antibodies to VLA-1 and VLA-2 localized these complexes in vinculin-positive adhesion plaques. In contrast, the receptor complexes were not detected in adhesion plaques of cells attached to fibronectin- or laminin-coated substrates. These results indicate that melanoma cells express at least two different integrin-related collagen-binding receptor complexes that appear to mediate cell adhesion to collagen.
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PMID:Identification of integrin collagen receptors on human melanoma cells. 253 53

The integrin heterodimer VLA-2, previously known as a collagen receptor, is now shown also to be a laminin receptor. Adhesion of the human melanoma cell line LOX to laminin was inhibited by anti-VLA alpha 2 antibodies. Because VLA-2-mediated LOX cell attachment to laminin was not inhibited by digestion with collagenase, collagen contamination of laminin was not a factor. In addition, VLA-2 from LOX cells bound to immobilized laminin, and binding was disrupted by EDTA but not by Arg-Gly-Asp (RGD) peptides. VLA-3 also bound to laminin-Sepharose, although less avidly than VLA-2. Thus, at least four separate members of the integrin beta 1 subfamily serve as laminin receptors--i.e., VLA-2 and VLA-3 (this study) together with VLA-1 and VLA-6 (other reports). Whereas LOX and other cell lines used VLA-2 as both a laminin and collagen receptor, fibroblast VLA-2 mediated collagen but not laminin binding. Likewise, VLA-2 from platelets did not interact with laminin. Despite this functional discordancy, VLA-2 from laminin-binding and nonbinding sources was indistinguishable by all immunochemical and biochemical criteria examined. Thus, functional differences in VLA-2 may be due to cell type-specific modulation.
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PMID:The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. 255 34


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