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

Cell adhesion is a critical factor in the multistep process of tumour invasion. CD44 is one of the cell surface adhesion molecules responsible for interaction with hyaluronic acid, a component of the CNS extracellular matrix. The aim of the present study was to demonstrate whether alterations in the CD44 gene might account for different invasive behaviour. EcoRI restriction analysis by Southern blot hybridization revealed several additional hybridization signals in tissue specimens of two out of 16 patients with glioblastoma, indicating DNA rearrangements or point mutations, respectively, within the region of the CD44 gene. Expression patterns of CD44 isoforms in these two rearranged gliomas and in 28 other patients with malignant gliomas were analysed by RT-PCR. All cases displayed only the splice variant CD44H, which acts as hyaluronic acid receptor in glioma tumour cells. Tumour cell invasion was studied with Boyden chamber assays using hyaluronic acid as ligand and functional CD44H blocking antibody. Invasion of cells derived from those gliomas carrying the rearranged CD44 gene locus was decreased by about 50% compared with gliomas without rearrangement, indicating that the altered hybridization patterns in the two glioma samples influenced CD44H mediated glioma cell invasion through hyaluronic acid in vitro. Our results on CD44 isoform expression suggest that, in contrast to other solid tumours, gliomas seem to express only the CD44 variant. Genetic alterations within the CD44 gene might alter the binding domain of the receptor and thus account for different invasive behaviour in glioblastomas.
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PMID:Effect of changes in the CD44 gene on tumour cell invasion in gliomas. 936 62

Neurofibromatosis 2 (NF2) protein (merlin; schwannomin) is a tumor suppressor involved in tumorigenesis of NF2-associated and sporadic schwannomas and meningiomas. The protein shares the domain structure of three homologous proteins: ezrin, radixin and moesin (ERM). ERM proteins function as membrane organizers and may act as linkers between plasma membrane molecules, such as CD44 and ICAM-2, and the cytoskeleton. We analyzed the distribution and effects of transfected NF2 protein in COS-1, CHO and 293 cells, and endogenous NF2 protein in U251 glioma cells. The distribution was compared to ezrin, CD44 and F-actin. Both transfected and endogenous NF2 protein localized underneath the plasma membrane in a pattern typical of an ERM protein. In COS-1 transfectants, NF2 protein typically codistributed with ezrin but, in cells with poorly developed actin cytoskeleton, it replaced ezrin in filopodia and ruffling edges. NF2 protein colocalized with CD44, which in transfected cells accumulated into restructured cell membrane protrusions. The association of CD44 and NF2 protein was further suggested by binding of CD44 from cellular lysates to recombinant NF2 protein. Interaction between NF2 protein and the actin-containing cytoskeleton was indicated by partial colocalization, by cytochalasin B-induced coclustering, and by retention of NF2 protein in the detergent-insoluble fraction. Transfected NF2 protein induced morphogenic changes. The cells contained restructured membrane extensions and blebs, and CHO cells expressing NF2 protein were more elongated than control transfectants. In conclusion, NF2 protein possesses functional properties of an ERM family member.
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PMID:Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. 937 74

Sodium valproate (VPA) belongs to the group of simple branched-chain fatty acids and due its anticonvulsive activity is broadly applied in the treatment of epilepsy. We previously showed that VPA is able to induce cellular differentiation, to enhance immunogenicity and to inhibit proliferation of human neuroblastoma (NB) cells in vitro. Furthermore, we demonstrated that VPA inhibits proliferation, enhances neural cell adhesion molecule expression and decreases CD44 expression of human and rat glioma cells in vitro. In the present study we investigated the antitumoral effects of VPA on established human NB xenografts from UKF-NB-3 human NB cells in athymic (nude) mice. When the animals developed s.c. tumors of about 100 mm3 volume they were treated with 400 or 200 mg/kg/day VPA i.p. At the end of the treatment period (40 days) tumor volumes in animals treated with 400 and 200 mg/kg VPA were about 4- (p < 0.0001) and 2-fold (p < 0.0005) smaller than in the saline-treated control group, respectively. Histological examination of the remnant tumors of treated animals revealed induction of differentiation by induction of stroma-rich tumors and nodules that contained elongated NB cells. Pyknotic nuclei and apoptotic bodies indicated induction of apoptosis. We conclude that VPA is able to abrogate NB growth in vivo and may therefore be useful in the treatment of NB patients.
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PMID:Sodium valproate inhibits in vivo growth of human neuroblastoma cells. 943 39

The so-called nasal gliomas (nasal cerebral heterotopias) are rare, congenital, benign masses of neurogenic origin with intra or extranasal location, or both. An intranasal case is reported in a 7-month-old infant who successfully underwent surgery with the intranasal approach. The tumor had no intracranial extension and the child is free of disease after a three-year follow-up. Immunohistochemical study confirmed the glial (GFAP+) and neuronal (NSE+) nature of the cells composing the mass. In addition to the clinical behavior, the benign nature of the tumor is also indicated by the negativity of Ki67 (MIB-1) and p53 proliferation markers as well as by CD44 negativity. As far as we know, this is the first reported case of nasal glioma subjected to immunohistochemical investigation of proliferation activity.
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PMID:So-called nasal glioma: case report with immunohistochemical study. 967 25

Cell adhesion receptors of the integrin superfamily, CD44, and adhesion receptors of the immunoglobulin superfamily are expressed by high-grade astrocytic tumors of the central nervous system. These receptors are critical for the invasion of these tumors in the nervous system. Glioma cells utilize these receptors to adhere to and migrate along the components of the extracellular matrix, which is uniquely distributed and regulated within the brain and the spinal cord. For this reason, glioma cell invasion into the adjacent brain tissue is dependent on the interaction of glioma cells with the extracellular matrix. The receptor-ECM component interaction is discussed, focusing on the role of cell adhesion molecules of the integrin family and CD44 in glioma cell adhesion and invasion.
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PMID:ECM-mediated glioma cell invasion. 984 Aug 3

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

Recently we were able to show that valproic acid (VPA) induces growth-arrest and differentiation of human neuroblastoma cells. Hence we investigated in vitro the antitumoral effects of VPA on malignant gliomas by determining cell proliferation and expression of CD56 and CD44 of human T98G, A172, 85HG66, 86HG39 and rat C6 cell lines. VPA at concentrations ranging from 0.1 to 1 mM strongly inhibited proliferation of A172, 86HG39, 85HG66 and C6 cells in a dose-dependent manner, whereas T98G cell growth remained unchanged. All human glioma cells were highly positive for CD44, whereas CD56 was differently expressed. After 7 days of incubation with 1mM VPA CD56 expression was markedly increased in T98G, A172 and 85HG66 cells, whereas CD44 expression was decreased in all human cell lines. These data suggest that VPA has antitumoral effects on malignant glioma cells. Therefore we consider VPA as a potent therapeutic agent for treatment of these tumors.
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PMID:Valproic acid inhibits proliferation and changes expression of CD44 and CD56 of malignant glioma cells in vitro. 985 43

Astrocytic tumours of the central nervous system express cell adhesion receptors of the integrin superfamily, CD44 and adhesion receptors of the immunoglobulin superfamily. Glioma cells utilize these receptors to adhere to and migrate along components of the extracellular matrix (ECM), which is uniquely distributed and regulated within the brain and the spinal cord. For penetration into healthy brain tissue a number of proteases are expressed, which degrade proteins of the extracellular matrix. Thus, glioma cell invasion into the adjacent brain tissue is dependent on the interaction of glioma cells with the extracellular matrix and the subsequent destruction of matrix barriers. There is a critical balance between expression of various adhesion receptors and proteases. The tight regulation of critical levels of proteases and receptors expressed by glioma cells or other cells is necessary for the "physiological" behaviour of glioma cells. Shifts in the balance of protein expression determine glioma cell behaviour in their micro-environment and can initiate or influence the complex process of glioma cell invasion. The complex receptor-ECM interaction in glioma cell invasion is discussed focussing upon the role of integrin receptors and matrix-metalloproteinases. Influencing these molecules or their regulation may lead to novel therapeutic approaches in the treatment of malignant glioma.
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PMID:Cell-extracellular matrix interaction in glioma invasion. 1021 87

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

The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigated expression of the hyaluronic acid receptor CD44 protein in five human (T98G, A172, U87MG, 86HG39, 85HG66) and two rat (C6, 9L) glioma cell lines. Influence of anti-CD44 antibody and hyaluronidase-preincubation on the HA-binding was determined using HA/BSA (bovine serum albumin)-coated culture plates. While all gliomas were highly positive for CD44 with no differences in the number of positive staining cells, median fluorescence intensity decreased as follows: C6>T98G>9L>85HG66> 86HG39>A172>U87MG. Using HA/BSA coated culture plates the relative levels of specific adhesion to HA were determined as T98G>A172>9L>86HG39>U87MG> 85HG66. C6 cells failed to bind HA specifically. Incubation with anti-human-CD44 MAb significantly decreased HA-adhesion of T98G, A172, 85HG66 and U87MG human glioma cells. However the binding capacity was completely blocked only in 85HG66 cells. The three other cell lines kept a specific HA-adhesion after saturation of the receptor. Hyaluronidase pretreatment markedly enhanced HA-adhesion of C6 and 9L rat glioma cells. These results suggest that (i) HA-adhesion of malignant glioma cells is mainly, but not only, mediated by CD44, (ii) expression of CD44 does not correspond with adhesion capacity and (iii) cell-bound glycosaminoglycans may influence glioma cell adhesion to extracellular HA.
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PMID:CD44 expression and hyaluronic acid binding of malignant glioma cells. 1039 Jan 50


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