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)

Local tumour-cell invasiveness, which is a major morphological feature of astrocytomas, involves interactions between tumour cell and extracellular matrix (ECM) including adhesion, proteolysis, and migration of tumour cells through the locally modified microenvironment. These interactions are mediated by cell/cell and cell/substrate adhesion molecules. We have earlier demonstrated that the adhesion molecule CD44 is expressed on gliomas and plays a role in adhesive interactions between glioma cells and a wide range of ECM components. In the present in vitro study we have further investigated the possible role of CD44 in subsequent stages of cell/ECM interactions-spreading and migration, using the GCCM anaplastic astrocytoma cell line. We have demonstrated that cell spreading is more effective on fibronectin (FN) than hyaluronan (HA) with a mean cell perimeter of 185 microns when cells are grown on FN as compared to 66 microns on HA. Antibody blockade experiments indicated that CD44 is not involved in cell spreading on either substrate. In the in vitro migration assay the tumour cells displayed a 2.5 fold greater migration rate through HA-coated as compared to FN-coated polycarbonate membranes. Blocking of CD44 by specific monoclonal antibody resulted in an inhibition of migration by 56% on HA providing evidence that CD44 plays a role in migration of astrocytoma cells in vitro.
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PMID:CD44 is involved in migration but not spreading of astrocytoma cells in vitro. 913 32

The regulation of adhesion molecule expression in malignant gliomas by tumor necrosis factor-alpha (TNF) and soluble TNF receptors (TNFR) was examined in the malignant glioma cell line A-172 and in 2 primary glioblastoma cell cultures (LA-492 and LA-567). A-172 cells expressed only the p55 TNF receptor transcripts and protein. The 2 primary cell cultures expressed both the p55 and p75 TNF receptors. In A-172 cells and in 1 of 2 primary glioma cell cultures, TNF upregulated the expression of ICAM-1 and VCAM-1, A-172 and both primary glioma cultures also shed their TNF receptors in the absence of activation by stimulating agents. Soluble p55 (sp55) receptors, but not soluble p75 (sp75) receptors, were found to reduce the TNF induced VCAM-1 and ICAM-1 expression in both the glioma cell line and the primary cell culture. Immunostaining of malignant glioma sections confirmed the presence of soluble TNFR and adhesion molecule expression in glioma cells in situ. These data suggest that soluble TNF receptors may play a role in the mechanism by which malignant gliomas downregulate the effects of infiltrating immune-competent cells.
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PMID:Soluble TNF-alpha receptors are constitutively shed and downregulate adhesion molecule expression in malignant gliomas. 914 67

The role of adhesion molecule L1 in synapse formation was examined by transient transfection of L1 cDNA in neuroblastoma x glioma hybrid NG108-15 cells. L1 overexpression was found in approximately 50% of the transfected NG108-15 cell population. Neurite outgrowth induced by 0.25 mM dibutyryl cyclic AMP (cAMP) was much greater in L1-transfected NG108-15 cells than that in nontransfected and mock-transfected cells. The proportion of cells with neurites and the number of neurites per cells were increased in L1-transfected cells after 2 days of dibutyryl cAMP treatment. The proportion of cells with branched neurites and the average length of neurites were higher at day 4. A significantly higher rate of synapse formation with myotubes was apparent in the late phase of coculture (days 4-7) in L1-transfected cells than in control cells. The miniature end-plate potential frequency in myotubes was the same for the three types of NG108-15 cells. These results show that overexpression of L1 in NG108-15 cells facilitates synaptic connections by enhancing branching and elongation of neurites induced with dibutyryl cAMP, rather than by increasing probability of acetylcholine release.
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PMID:Overexpression of adhesion molecule L1 in NG108-15 neuroblastoma X glioma hybrid cells enhances dibutyryl cyclic AMP-induced neurite outgrowth and functional synapse formation with myotubes. 916 21

In this study the effect of interferon and anti-CD44 antibody on the invasiveness of mouse glioma G-26 cells was evaluated. We confirmed the glial nature of G-26 glioma cells (G-26) in vitro and in vivo using immunohistochemistry: G-26 stained strongly for S-100 and stained weakly for glial fibrillary acidic protein (GFAP). Immunohistochemical evaluation for CD44 adhesion molecule showed that G-26 was positive both in vitro and in vivo. Weakly positive punctate staining for CD44 was seen in the cytoplasm of all viable glioma cells and focally strong staining was observed in a membranous pattern in the invading glioma cells. Evaluation of untreated G-26 cells using an in vitro invasion assay showed that they were able to digest a Matrigel matrix and to invade through an 8 microns microporous membrane. Treatment of the G-26 glioma cells for 3-4 days with mouse interferon alpha/beta at 8 x 10(2) or 8 x 10(3) mu/ml resulted in a significant decrease of invasiveness: 68.8% (p < 0.05) and 32.8% (p < 0.001) of cells, respectively, remained invasive when compared to control. Treatment of G-26 with antibody to the CD44 adhesion molecule significantly decreased invasiveness with 39.4% (p < 0.001) of cells remaining invasive when compared to control. We feel that both of these approaches, each of which produced significant inhibition of G-26 glioma cell invasion should be further evaluated for their usefulness in antiglioma therapy.
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PMID:The effect of interferon and anti-CD44 antibody on mouse glioma invasiveness in vitro. 985 5

We established a protocol for the non-isotopic in situ detection of adhesion molecule CD44 messenger RNA (mRNA) in archival formalin-fixed paraffin-embedded sections of human surgical materials. Four brain tumor samples with different histopathologies (a metastatic adenocarcinoma, a metastatic squamous carcinoma, a glioblastoma and a craniopharyngioma) were thus studied using a 157 nt digoxigenin-labeled RNA probe complementary to the common mRNA region to all the CD44 isoforms. The CD44 transcript was detected in the cytoplasm of glioma and such epithelial tumor cells as metastatic carcinoma and craniopharyngioma. A competitive hybridization study confirmed the specificity of the CD44 probe. The optimization of critical conditions are also discussed. This protocol should therefore be useful in making an accurate evaluation of mRNA localization and may also facilitate the successful completion of extensive retrospective studies on a large number of archival samples.
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PMID:Non-isotopic in situ hybridization of CD44 transcript in formalin-fixed paraffin-embedded sections. 1023 50

Based on the hypothesis that adhesion molecules expressed on the surface of glioma cells mediate brain invasion, we examined the effect of CD24 on growth and migration of gliomas in vitro and in vivo. CD24, a glycosylphosphatidylinositol anchored, highly glycosylated adhesion molecule, is expressed in hematopoietic and neural cells. We found immunohistochemical expression of CD24 in human glioblastomas. We then established a clone from C6 rat glioblastoma cells, where mouse CD24 (also called heat stable antigen) is under control of a tetracycline-responsive promoter. In the presence of tetracycline (1 microg/ml) CD24 was downregulated by 20-fold. In vitro migration assays were performed on a basement membrane preparation (matrigel) and on myelin, the main substrates of in vivo glioma migration. While the cells were more motile on matrigel as compared with myelin, no relation between CD24 expression and motility was observed. We then transplanted the C6 clone into the striatum of nude mice and regulated CD24 expression via tetracycline in the drinking water (1 mg/ml). After 3 weeks, CD24 positive tumors of mice getting no tetracycline showed diffuse invasion of tumor cells in a brain area 10-fold larger than in CD24-suppressed tumors of mice receiving tetracycline. These data show that CD24 stimulates migration of gliomas in vivo and they suggest a role for this adhesion molecule in diffuse brain invasion of human gliomas.
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PMID:CD24 promotes invasion of glioma cells in vivo. 1044 4

We have previously reported that invasiveness of mouse glioma G-26, which expresses CD44 adhesion molecule, was inhibited in vitro following treatment with anti-CD44 antibody or mouse interferon alpha/beta (MuIFN alpha/beta). Here, we evaluated whether the expression of transmembrane CD44 adhesion molecule and/or secretion of extracellular matrix metalloproteinases (MMPs) were affected when glioma cell invasion was inhibited. Flow cytometric evaluation of CD44 adhesion molecule expression in G-26 glioma using anti-CD44 antibody, confirmed that G-26 cells were CD44+. Following 3-day treatment with MuIFN alpha/beta at 8 x 10(2) or 8 x 10(3) IU/ml of glioma cells, the expression of CD44 was not significantly affected as reflected by CD44+ cell number and fluorescence intensity. The pretreatment of glioma cells for 1 day with anti-CD44 antibody resulted in a 30-60% decrease of CD44 expression. This coincided with significantly (p < 0.05) lower cell activity as judged by MTT assay for mitochondrial activity. The zymographic evaluation of MMP activity in the G-26 glioma cell culture showed a high level of the active form of MMP-2. This level of MMP-2 was decreased following 3 day treatment of G-26 glioma cells with either 8 x 10(2) or 8 x 10(3) IU/ml of MuIFN alpha/beta but only the latter concentration produced statistically significant 55% decrease. However, following a 1 day treatment of G-26 glioma cells with anti-CD44 antibody, the level of active MMP-2 form was not significantly affected. These findings indicate that while the inhibitory effect of IFN on glioma invasion was accompanied by a decreased level of the active form of MMP-2 released extracellularly, the expression of the transmembrane CD44 adhesion molecule was not affected. Conversely, anti-CD44 antibody pretreatment of G-26 glioma, which led to the inhibition of glioma invasion, resulted in decreased CD44 expression and lower cell activity but had no effect on the MMP-2.
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PMID:CD44 expression and MMP-2 secretion by mouse glioma cells: effect of interferon and anti-CD44 antibody. 1120 62

Heat shock proteins are recognized as significant participants in immune reactions. In this study, we have demonstrated that the cell surface presentation of MHC class I antigen was increased in tandem with increased heat shock protein 70 (HSP70) expression and the immunogenicity of rat T-9 glioma cells was enhanced by hyperthermia. T-9 cells showed growth inhibition for 24 h after the heat treatment at 43 degrees C for 1 h in vitro, but then resumed a normal growth rate. HSP70 expression reached a maximum at 24 h after heating. Flow cytometric analysis revealed a significant increase in MHC class I antigen on the surface of the heated cells. The augmentation of MHC class I surface expression started 24 h after heating and reached a maximum 48 h after heating. The expression of other immunologic mediators, such as intracellular adhesion molecule-1 (ICAM-1) and MHC class II antigens, did not increase. In an in vivo experiment using immunocompetent syngeneic rats (F344), growth of the heated T-9 cells, with augmentation of MHC class I antigen surface expression, was significantly inhibited, while the cells grew progressively in nude rats (F344/N Jcl-rnu). Furthermore, compared with lymphocytes from non-immunized (PBS only injection) rats or rats injected with non-heated T-9 cells, the splenic lymphocytes of the rats in which the heated T-9 cells were injected displayed specific cytotoxicity against T-9 cells. These results suggest that HSP70 is an important modulator of tumor cell immunogenicity, and that hyperthermic treatment of tumor cells can induce the host antitumor immunity via the expression of HSP70. These results may benefit further efforts on developing novel cancer immunotherapies based on hyperthermia.
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PMID:Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia. 1177 73

L1 is an adhesion molecule of the immunoglobulin superfamily expressed by several types of cancer, including gliomas. It has been shown that L1 can act as chemoattractant to glioma cells, while the effects of L1 expressed by glioma cells themselves are unknown to date. We established a C6 rat glioma clone, conditionally expressing murine L1 under control of a tetracycline responsive promoter. In vitro experiments revealed increased adhesion on matrigel as well as increased intercellular adhesion in the presence of L1, whereas no L1-dependent effects on proliferation or migration on either matrigel or myelin were observed. In vivo experiments using transplantation into nude mouse striatum, where L1 expression by glioma cells was regulated by tetracycline via drinking water, did not show effects of L1 on tumor size or brain invasion. Our data suggest that L1 expressed on the surface of glioma cells increases cell-matrix and intercellular adhesion, but has no apparent effects on proliferation and invasion.
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PMID:L1 expressed by glioma cells promotes adhesion but not migration. 1194 8

FasL has been shown to induce angiogenesis in vivo, however, the mechanism remains to be determined. We have previously shown that Fas ligation induces expression of chemokines such as interleukin-8 by human astrogliomas, which may partially explain the in vivo angiogenic property of FasL. Intercellular adhesion molecule (ICAM)-1 is increased in various human tumors, and is thought to be involved in the processes of metastasis and angiogenesis. We demonstrate that Fas ligation induces ICAM-1 expression at the mRNA and protein levels in human astroglioma cells. Studies using Boc-D-Fmk, a pharmacological inhibitor, show that caspase activation is required for Fas-mediated ICAM-1 induction. To study the in vivo expression of Fas and ICAM-1, human low-grade astrogliomas and glioblastoma multiforme (GBM) samples were examined by ELISA for Fas and ICAM-1. Human GBM samples express higher levels of Fas compared to normal control brain, which correlates with increased ICAM-1 expression. These findings suggest that Fas ligation on human glioma cells leads to the induction of ICAM-1 expression, which involves caspase cascade signaling pathways.
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PMID:Induction of intercellular adhesion molecule-1 by Fas ligation: proinflammatory roles of Fas in human astroglioma cells. 1461 40


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