Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monosialoganglioside GM1 can potentiate the neuritogenic activity of media conditioned by several cell types: neonatal glia, C6 glioma, embryonic chick heart or skeletal muscle and the rat myogenic line L6. To probe further the neuritogenic activity of conditioned media (CM), 5 mouse monoclonal antibodies (mAbs) against GM1, designated B6, C3, C4h2, D1 and D3 were incorporated individually into nutrient medium (NM) supplemented with CM prior to incubation with sensory ganglia. Nine-day embryonic chick dorsal root ganglia were explanted onto collagen-coated coverslips and incubated at 35 degrees C for 5 h in NM supplemented with 150 micrograms/ml GM1. After washing with NM, the explants were re-fed with NM + CM containing 20% mAb and cultured for an additional 43 h. The resultant neuritogenesis was evaluated microscopically by determining mean neurite number and length of randomly mixed cultures. The 5 antibodies differed in their capacities to inhibit CM-mediated neuritogenesis of these primed target cells. D1 and D3 were most effective in reducing neurite length and number produced by all sources of the CM, while C3 and C4h2 were intermediate in their inhibition of neurite initiation (number). The effect of B6 on neurite initiation and elongation was the least. The ability of these mAbs to inhibit neuritogenic activity of CM derived from both glial and myogenic tissue suggests that gangliosides play a basic role in neuronal development. The differing responses elicited by the individual mAbs may reflect a relationship between the structural complexity of the GM1 molecule and the neuritogenic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of conditioned media-mediated neuritogenesis of sensory ganglia by monoclonal antibodies to GM1 ganglioside. 340 9

The ability of gangliosides to potentiate nerve growth factor (NGF)-independent trophic agents was determined by examining the capacity of an exogenous mixture of bovine brain gangliosides (BBG) and the monosialoganglioside GM1 to enhance the neuritogenic action of conditioned media (CM). CM were prepared with cultures of C6 glioma cells, neonatal rat astroglial cells, rat L6 myoblasts and chick embryonic skeletal muscle. Chick embryonic (9 day) dorsal root ganglia (DRG) were cultured on collagen-coated surfaces. The nutrient media with serum added or serum-free N1 medium were supplemented with 50% of one of the CM with or without BBG (150 micrograms/ml) or GM1 (150 micrograms/ml). The neuritogenic responses of DRG 48 h in vitro were evaluated microscopically on the basis of neurite length and number. The neurite promoting action of the factor(s) present in the various CM was potentiated by BBG or GM1 and resulted in increased neurite length and number.
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PMID:Ganglioside potentiation of NGF-independent trophic agents on sensory ganglia. 341 44

The growth of PC12 cells on a collagen substratum or on monolayers of several non-neuronal cell types was studied by measuring nerve growth factor (NGF)-dependent increases in the expression of a 150 X 10(3) (Mr) neurofilament protein subunit and the membrane glycoprotein Thy-1. Both responses were found to be greatly suppressed in cultures of fibroblasts as compared to the C2 and G8-1 muscle cell lines and the C6 glioma cell line. This suppression was associated with an inhibition of NGF-dependent neuritic outgrowth from PC12 cells grown on fibroblast monolayers. There was no evidence that fibroblasts secrete soluble molecules that directly inhibit these responses or neutralize NGF. In addition, there was no difference in the neurofilament protein response from PC12 cells that had been treated with NGF prior to coculture, and the now primed PC12 cells readily extended axons over fibroblast monolayers. These data demonstrate that cell-cell and/or cell-matrix interactions can modulate biochemical responses to NGF and suggest that responsiveness of neuronal cells to environmental cues is not immutable. Control of the latter may be at the level of expression of receptor molecules for cell-surface- or matrix-associated macromolecules and a similar mechanism operating during development could play a role in growth cone guidance.
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PMID:Cell-cell interactions modulate the responsiveness of PC12 cells to nerve growth factor. 350 97

Five primary and 3 established human glioma cell lines were cultured with ascorbate and examined for expression of extracellular matrix components. All lines except C6 expressed collagen as assessed by silver impregnation, immunofluorescence and lectin staining and expressed laminin and fibronectin. None expressed a lectin marker for endothelial cells. Both epithelial and mesenchymal collagens were expressed. While extracellular components of glioma lines resembled those of fibroblasts more closely than other cell types, subtle differences between gliomas and fibroblasts were present. These included more laminin and collagen type-IV antigenic reactivity and more 11-12 nm diameter extracellular fibrils from individual gliomas, and slight differences in spectra of low-molecular-weight extracellular proteins assessed by gel electrophoresis. One primary and two established glioma lines analysed for DNA content were aneuploid in contrast to diploid fibroblasts. Simultaneous expression of mesenchymal and epithelial markers suggests a dual differentiation potential of glioma cells. Results do not support an endothelial origin for cells cultured from gliomas.
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PMID:Products of cells cultured from gliomas. IV. Extracellular matrix proteins of gliomas. 351 74

We devised a model system to study the effects of extracellular matrix proteins on the malignant phenotype of an anaplastic glioma cell line, U 343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The leptomeningeal cells were then removed with base and detergent, leaving behind an extracellular matrix enriched in laminin, fibronectin, type I and IV collagen, and procollagen III. U 343 MG-A tumor cells planted on top of this normal extracellular matrix were profoundly growth inhibited compared with glioma cells grown on plastic alone. Glioma cells grown on the extracellular matrix developed multiple, slender processes and assumed a more differentiated astrocytic phenotype; immunostains for glial fibrillary acidic protein revealed a more extensive intracytoplasmic network of intensely staining filaments than in control glioma cells. When glioma cells grown on the extracellular matrix were analyzed by an enzyme-linked immunosorbent assay for glial fibrillary acidic protein, the amount of this intermediate filament per cell was increased 20-fold compared with glioma cells growing on plastic. The growth and differentiation of U 343 MG-A glioma cells in flasks coated with purified fibronectin or laminin was not significantly perturbed; however, glioma cell cultures grown in flasks coated with purified type I or IV collagen showed decreased cellular proliferation, stellate cell formation, and increased levels of glial fibrillary acidic protein per cell compared with glioma cells growing on plastic. Gelatin gel analysis showed that U 343 MG-A glioma cells growing on plastic secreted a 65,000-D metalloproteinase that was not secreted by glioma cells grown on the leptomeningeal extracellular matrix. We conclude that in this system, the extracellular matrix of a normal human leptomeningeal culture substantially inhibited the proliferation of and induced differentiation in an anaplastic glioma cell line. Our analysis of single components of the extracellular matrix suggests that these effects may be mediated in part by type I and IV collagen. The mechanism by which the leptomeningeal extracellular matrix inhibits glioma cell proliferation may be by diminishing tumor-associated protease secretion so that the degradation of extracellular matrix macromolecules in the tumor cell microenvironment is prevented and tumor cell migration becomes less likely.
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PMID:Inhibition of growth and induction of differentiation in a malignant human glioma cell line by normal leptomeningeal extracellular matrix proteins. 355 73

The distribution of type VI collagen was examined immunohistochemically in normal tissues and in 24 human gliomas and six medulloblastomas. Its localization in the neoplasms was compared with that of fibronectin and glioma-mesenchymal extracellular matrix (GMEM) glycoprotein. In normal non-neural tissues type VI collagen was demonstrated in the interstitial connective tissue and in some basement membranes. In normal brain it was localized to the vasculature, leptomeninges, and pial-glial membrane. In neoplasms type VI collagen and fibronectin codistributed in the vasculature and stromal connective tissue. The GMEM glycoprotein, as identified by monoclonal antibody (MAb) 81C6, and a related glioma-mesenchymal matrix antigen identified by MAb 2A6, were expressed not only in the tumor vasculature and connective tissue, but also within the tumor parenchyma in association with glioma cells. The staining intensity was variable in 20 malignant gliomas and weak to absent in two pilocytic astrocytomas and six medulloblastomas. An oligodendroglioma and ependymoma both expressed the 2A6 epitope, but staining with MAb 81C6 was weak to absent. The antigens identified by MAb 81C6 and MAb 2A6 represent the only recognized extracellular matrix components, other than proteoglycans, that are associated with glioma cells in vivo. As prominent constituents of the pericellular matrix, they may be involved in recognized matrix functions such as the modulation of cell adhesion and migration.
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PMID:Distribution of type VI collagen in human gliomas: comparison with fibronectin and glioma-mesenchymal matrix glycoprotein. 365 35

Cell lines derived from 3 different types of human tumor (e.g., squamous carcinomas, melanomas and gliomas) were examined for production of plasminogen activator activity and for attachment and spreading on various extracellular matrix components in the presence or absence of plasminogen. All of the squamous carcinoma and melanoma lines produced high levels of plasminogen activator activity. In contrast, 4 of 6 glioma lines had undetectable activity. Cells from all 3 tumor types attached and spread on fibrinogen-coated or fibrin-coated plastic dishes in the absence of plasminogen. In the presence of exogenous plasminogen, the attachment and spreading of the cells which produced high levels of plasminogen activator activity was inhibited. The plasminogen activator-deficient cells were much less sensitive to exogenous plasminogen. In the presence of plasminogen, attachment and spreading on fibronectin-coated dishes was also partially inhibited. In contrast, plasminogen had no effect on the attachment and spreading of the cells on type-I or -IV collagen, laminin or thrombospondin. Previous studies have shown that tumor-cell adhesion to the extracellular matrix depends on the synthesis of receptors for extracellular matrix components or on the synthesis of extracellular matrix components themselves. The present study shows that, in addition, the production of enzymes which are capable of degrading these components also influences tumor-cell adhesion to extracellular matrix moieties.
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PMID:Plasminogen activator production by human tumor cells: effect on tumor cell-extracellular matrix interactions. 369 23

In order to elucidate mechanisms of contrast enhancement on computed tomography observed in non-glial tumors, tumors vessels were studied with conventional ultrathin section and freeze-fracture replica techniques. The materials were obtained from surgically removed specimens in 19 cases of tumors (6 of meningioma, 6 of hemangioblastoma, 5 of pituitary adenoma, and 2 of acoustic neurinoma). The following results were obtained. The common findings of these non-glial tumor vessels in ultrathin preparations were surface infoldings, increased pinocytotic vesticles and many fenestrations of endothelial cells, irregularity of basal laminae, and enlarged perivascular spaces. In freeze-fracture replicas of vascular endothelium, pinocytotic vesicles and fenestrations were 22 and 26 per micron2 on the average respectively. Tight junctions between endothelial cells were composed of one or two strands which appeared to be a discontinuous array of particles. As for the each non-glial tumor, menigiomas showed endothelial thickness and finger-like projections, variable lengths of tight junctions and marked enlargement of perivascular space which contained many collagen fibrils. Thinning of endothelium and many fenestrations were observed in hemangioblastomas, pituitary adenomas, and acoustic neurinomas. Fenestrations were most frequently observed in pituitary adenomas. The results indicate that extravasation of contrast material through fenestrations has an important role in marked contrast enhancement of non-glial tumors, in addition to the osmotic opening of tight junctions by contrast material. The irregular basal lamina and large perivascular space may also contribute to an increased extravasation of contrast material.
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PMID:[Ultrastructure of capillary permeability in human brain tumors. 3: Mechanisms of contrast enhancement in non-glial tumors]. 370 29

Thrombospondin (TSP) induced the attachment and spreading of human squamous carcinoma cells on plastic culture dishes and dishes coated with type I or type IV collagen. Increased adhesion was detected as early as 15 min after treatment. Dose-response studies indicated that 1-5 micrograms of TSP per 35 mm (diameter) culture dish was sufficient to induce a response and that a half-maximal response occurred at 10 micrograms of TSP/dish. The squamous carcinoma cells synthesized TSP as indicated by biosynthetic labeling experiments. TSP was secreted (or shed) into the culture medium by these cells and also became bound to the cell surface. TSP also promoted adhesion of human keratinocytes, fibroblasts and fibrosarcoma cells but did not induce attachment or spreading of human melanoma or glioma cells, although these cells did respond to laminin.
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PMID:Thrombospondin-induced attachment and spreading of human squamous carcinoma cells. 377 94

Efforts to determine the factors responsible for reversing malignancy in the central nervous system may not only increase our understanding of the growth of primary human brain tumors, but may eventually prove to be of therapeutic benefit as well. We therefore devised a model system to study the effects of extracellular matrix (ECM) proteins on the malignant phenotype of an anaplastic glioma line, U-343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The pia-arachnoid cells were then removed with detergent and base, leaving behind an ECM enriched in laminin, fibronectin, types I and IV collagen, and procollagen III. U-343 MG-A tumor cells planted on top of this normal ECM were profoundly growth inhibited, developed multiple slender cytoplasmic processes similar to those of normal astrocytes, and expressed more GFAP per cell than did tumor cells growing on plastic alone. The growth of U-343 MG-A tumor cells in flasks coated with purified fibronectin or laminin was not significantly inhibited. However, U-343 MG-A cultures grown in flasks coated with type I or IV collagen showed decreased cellular proliferation and altered cell morphology. Conditioned medium from U-343 MG-A tumor cells growing on plastic alone contained a 64 kD activated metalloprotease. U-343 MG-A tumor cells growing on the pia-arachnoid ECM do not demonstrate such proteolytic activity. We conclude that the tumor cell microenvironment is extremely important in modulating the growth and differentiation of an anaplastic glioma cell line.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The K.G. McKenzie award lecture--1986. Effects of extracellular matrix proteins on the growth and differentiation of an anaplastic glioma cell line. 377 29


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