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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown both in vivo and in culture that astrocytes communicate with brain microvessel endothelial cells (BMECs) to induce many of the blood-brain barrier characteristics attributed to these unique cells. However, the results using cultured cells are conflicting as to whether this communication is dependent upon cell-cell contact. In this study we used primary cultures of bovine BMECs grown as monolayers on polycarbonate filters to study the formation of the barrier in vitro and examine its modulation by rat C6 glioma cells. Effects were examined by treating postconfluent BMEC monolayers with medium conditioned continually by C6 cells from the basolateral side to mimic the in vivo orientation. Cell monolayer integrity was assessed using electrical resistance and by measuring diffusion of uncharged molecules. BMEC monolayers form a functionally polarized and leaky barrier, with maximal resistance of 160 omega . cm2 and significant flux of molecules of molecular weight less than 350 Da. Treatment with rat or human astroglioma cells rather than pericytoma cells or transformed fibroblasts results in a concentration-dependent 200-440% increase in electrical resistance and a coincident 50% decrease in permeability to sucrose and dextran (70 kDa). The decrease in passive diffusion is most likely due to a change in tight junctions and not to transcellular vesicular traffic. The findings support that astroglioma cells release one or more signals that are required for cultured BMECs to express a "differentiated" phenotype associated with a tighter barrier, increased gamma-glutamyl transpeptidase activity, and decreased pinocytic activity. The relative ease and quickness of this culture system makes it amenable to studies on cell-cell interaction and regulation of barrier maintenance.
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PMID:Permeability of bovine brain microvessel endothelial cells in vitro: barrier tightening by a factor released from astroglioma cells. 134 2

Primary cultures of brain capillary endothelial cells (BCECs) cocultured together with astroglia cells were used to investigate the induction of blood-brain barrier (BBB) characteristics in vitro. By immunofluorescence, histochemical staining, two-dimensional gel electrophoresis and enzyme activity tests we are able to show that BCECs in vitro loose typical blood-brain barrier properties but not their common endothelial phenotype. Astrocytes induce the expression of the blood-brain barrier characteristic enzymes gamma-glutamyltranspeptidase and alkaline phosphatase but only in a coculture system with direct cell to cell contact between BCECs and astroglia cells. C6-glioma cells also re-establish the BBB phenotype but were less effective compared to astrocytes. The susceptibility of the BCECs to an astroglial stimulus depends on the proliferative state of the BCECs.
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PMID:Development of an in vitro cell culture system to mimic the blood-brain barrier. 135 19

The blood-brain barrier (BBB) in mammals is created and maintained by cerebral endothelial cells (cEC) that express specialized functional properties, including intercellular tight junctions, absence of fenestrae and specific membrane transport systems. It has been proposed that the differentiation of these characteristics, acquired during brain development, is controlled by the neural environment. Co-culture experiments of cloned cEC with astroglial cells, C6 glioma cells and cortical neurons, with plasma membranes or conditioned media of these cells, were used to study induction of some BBB characteristics in vitro. Activities of Na+,K(+)-ATPase and gamma-glutamyl transpeptidase (GGTP), an enzyme responsible for amino acid transport across the BBB, were taken as parameters for BBB function. Co-culture of cEC with C6 glioma cells caused a two-fold increase in GGTP activity and this activity was likewise amplified by incubation with plasma membrane fractions derived from C6 glioma cells, embryonic brain cells and cortical neurons; conditioned media (soluble factors) had no effect. Na+,K(+)-ATPase activity, estimated from the ouabain inhibitable fraction of 86Rb uptake, was increased by about 90% in cEC incubated with C6 glioma plasma membranes. We propose from these data that both neurons and glial cells confer BBB characteristics on cEC via cell-cell contact.
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PMID:Glial cells and neurons induce blood-brain barrier related enzymes in cultured cerebral endothelial cells. 167 6

Primary cultures of brain capillary endothelial cells (BCECs) were used to investigate the induction of blood-brain barrier (BBB) characteristics in vitro. Enzymatic activities of gamma-glutamyltranspeptidase (gamma-GT) and alkaline phosphatase (ALP) were taken as indicators for the expression of the BBB phenotype. We were able to show that a coculture system with a direct cell-cell contact between astroglial cells and BCECs is the necessary precondition for an increase of these enzyme activities that are lost in pure BCEC cultures. Coculture with both astrocytes and C6-glioma cells reestablishes the BBB phenotype whereas conditioned media as well as an astrocyte-derived extracellular matrix were ineffective. The susceptibility of the BCECs to an astroglial stimulus depends on the proliferative state of the BCECs. Cells in an early highly proliferative culture phase were stimulated to express an enzymatic activity level similar to the in vivo situation. Confluent BCEC monolayers were not induced at all. With the ALP we observed a spatial induction within a BCEC colony. Astrocyte-induced ALP activity was first observed at an outer belt of BCEC colonies in direct contact with the astrocyte layer. However, this signal is transferred to the center of the colony with time in culture. We conclude that direct contact of BCECs with astroglial cells is necessary for the induction of the BBB phenotype in cultured BCECs and that this signal may be transferred from induced to noninduced BCECs.
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PMID:The susceptibility of cerebral endothelial cells to astroglial induction of blood-brain barrier enzymes depends on their proliferative state. 171 32

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.
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PMID:Induction of tumor degeneration by sodium benzylideneascorbate. 174 10

Human microvessels were isolated and cultured from non-neoplastic cerebral tissue specimens resected for the treatment of seizure disorders and from malignant glial tumors. After 1-2 weeks, cobblestone patterned plaques of cells were isolated and cultured from these microvessels. Cell lines positive for Factor VIII antigen and negative for glial fibrillary acidic protein were designated as endothelium. Endothelium from both tissue sources produced gamma-glutamyl transpeptidase in response to glial cell conditioned media. Tumor derived microvessel endothelium had decreased longevity in culture when compared to normal microvessel endothelium. Tumor derived endothelium also formed less extensive intercellular junctional complexes in vitro. The isolation and characterization of human cerebral microvessel endothelium derived from non-neoplastic tissue and glial tumors may lead to a further understanding of the role of endothelium in tumor growth and vascular permeability alterations.
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PMID:Human cerebral endothelium: isolation and characterization of cells derived from microvessels of non-neoplastic and malignant glial tissue. 211 73

The transport of radiolabeled L-glutamic acid by LRM55 glioma cells in culture was examined. Time course studies indicated that L-[3H]glutamic acid is rapidly accumulated, and then 3H is lost from the cell, presumably in the form of glutamate metabolites. Kinetic analysis of L-glutamate uptake provided evidence for two components of transport. A low affinity component was found to persist at 0 to 4 degrees C and was not saturable, influx being proportional to the substrate concentration. A high affinity component, resolved by subtraction of the influx at 0 to 4 degrees C, followed Michaelis-Menten kinetics having a Km of 123 microM and a Vmax of 2.99 nmol/min/mg of protein. The transport system was highly substrate-specific: At least 27-fold larger concentrations of the most potent analogues--cysteic acid, cysteine sulfinic acid, and L-aspartic acid--were required to compete effectively with glutamate. Second, the system was not severely affected by exposure to inhibitors of oxidative phosphorylation or gamma-glutamyltranspeptidase. Third, only 65% of the high affinity uptake was dependent upon the presence of sodium, the other 35% being dependent upon chloride. These observations were supported by the findings that uptake was only partially inhibited by ouabain and quite effectively reduced by several inhibitors of chloride transport. The results of this study provide information on the properties of low affinity glutamate transport, as well as the first description of sodium-independent, chloride-dependent high affinity glial transport. The high affinity component of influx is stimulated by elevated potassium and inhibited by several pharmacological agents. The sodium independence of a significant proportion of high affinity glutamate transport suggests that glutamate binding studies done in sodium-free medium with intact cells may be confounded by a considerable amount of intracellular uptake.
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PMID:Characterization of L-glutamic acid transport by glioma cells in culture: evidence for sodium-independent, chloride-dependent high affinity influx. 620 76

Rat brain microvessel endothelial cells were immortalized by transfection with a plasmid containing the E1A adenovirus gene. One clone, called RBE4, was further characterized. These cells display a nontransformed phenotype and express typical endothelial markers, Factor VIII-related antigen and Bandeiraea simplicifolia binding sites. When RBE4 cells were grown in the presence of bFGF and on collagen-coated dishes, confluent cultures developed sprouts that extend above the monolayer and organized into three-dimensional structures. The activity of the blood-brain barrier-associated enzyme, gamma-glutamyl transpeptidase (gamma GTP), was expressed in these structures, not in the surrounding monolayer. Similar results were obtained with the microvessel-related enzyme alkaline phosphatase (ALP). Addition of agents that elevate intracellular cAMP reduced the formation of three-dimensional structures, but every cell inside the aggregates still expressed gamma GTP and ALP activities. Such structures, associated with high levels of gamma GTP and ALP activities, were also induced by astroglial factors, including (1) plasma membranes from newborn rat primary astrocytes or rat glioma C6 cells, (2) C6 conditioned media, or (3) diffusible factors produced by primary astrocytes grown in the presence of, but not in contact with RBE4 cells. RBE4 cells thus remain sensitive to angiogenic and astroglial factors for the expression of the blood-brain barrier-related gamma GTP activity, as well as for ALP activity, and could constitute the basis of a valuable in vitro model of the blood-brain barrier.
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PMID:Regulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities in immortalized rat brain microvessel endothelial cells. 790 23

Glial cells have been shown to induce enzyme activities, which are characteristically high in brain capillaries, in cerebral and non cerebral endothelial cells in culture. We evaluated the activity of gamma-glutamyl transpeptidase (gamma GT) in freshly isolated (ex vivo) bovine blood (BEC) and lymphatic (LEC) endothelial cells. We also tested the effect of C6 glioma cell conditioned medium (GCM) on gamma GT activity of BEC and LEC in primary culture. Ex vivo BEC had a high gamma GT activity, only 9% of which was retained in culture. After exposure to GCM, however, gamma GT activity of cultured BEC was twofold higher than with control medium. By contrast gamma GT activity was extremely low in ex vivo LEC and did not significantly increase in cultured LEC exposed to GCM. These data show that the basal levels of gamma GT are markedly different in BEC and LEC and also that, unlike BEC, LEC are not capable of producing more gamma GT in response to glial stimulation.
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PMID:Glioma cells induce gamma-glutamyl transpeptidase activity in cultured blood but not lymphatic endothelial cells. 878 Jul 30

Increased expression of gamma-glutamyltransferase (GGT) has been detected in a range of human malignancies and is thought to be involved in neoplastic proliferation and treatment resistance. Since GGT expression and its role in malignant glioma biology remain largely unknown, we investigated this phenomenon by immunostaining 26 higher-grade human astrocytic gliomas (WHO grades III and IV) with a monoclonal anti-GGT-antibody (138H11). Further, human pancreatic GGT cDNA was used for liposome-mediated transfection of 9L gliosarcoma cells. GGT-expressing and control 9L cells were cultured in media containing different amounts of essential amino acids and/or cytotoxic agents. Cell viability was evaluated by microplate MTT assay. Immunohistochemical staining of tumor specimens demonstrated that GGT expression is a frequent feature of higher-grade human astrocytic gliomas, but not of normal brain tissue. Human tumors were strongly GGT-positive in 6 of 7 cases of grade III astrocytoma, and in 12 of 19 grade IV astrocytoma (glioblastoma multiforme, GBM) cases. In the cell culture model, 9L-GGT cells had a growth advantage over control cells in cysteine-deficient medium. but not in standard or glutamine-free medium. No significant difference in numbers of viable cells of either clone was found in media containing the alkylating drug BCNU (5-200 microg/ml). In conclusion, GGT is expressed in a high percentage of human WHO grade III astrocytomas and GBM, but not in normal brain tissue. This molecule seems to give neoplastic cells a moderate growth advantage under in vivo conditions.
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PMID:Gamma-glutamyl transferase expression in higher-grade astrocytic glioma. 1150 14


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