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

Using a fibrin-agarose-overlay technique, high levels of plasminogen-dependent fibrinolytic activity have been demonstrated in cell lines derived from an ethylnitrosourea-induced glioma of the rat brain. Cell lines derived from normal adult rat brain showed only low levels of activity. The degree of lysis produced by a cell line was dependent on the average number of cells per colony, and a different pattern of response was observed for tumour and normal cell lines. A good positive correlation existed between the level of fibrinolytic activity, growth in agar and tumourigenicity of a cell line. Fibrinolytic activity was associated with cell lines derived at various times in the latent period, before the appearance of a visible tumour. Many cell lines derived from rat brains at 57-60 (E7), 90-91 (E8) and 111-112 (E6) days after transplacental exposure to ethylnitrosourea showed fibrinolytic activity, and in the latter group the close association with growth in agar and tumourigenicity was also demonstrated. Results from cell lines derived in the E7 and E8 experiments indicated that the possession of fibrinolytic activity preceded the ability of cells to form colonies in agar.
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PMID:Fibrinolytic activity of cultured cells derived during ethylnitrosourea-induced carcinogenesis of rat brain. 63 21

The occurrance and significance of important carcinofetal antigens other than AFP and CEA are reported. These included the alpha 2 H-protein which is produced in the liver and increases in serum of patients with various tumors, the fetal sulphoglycoprotein antigen FSA from the gastric juice of patients with gastric cancer, the carcinoplacental alkaline phosphatase (REGAN-isoenzyme)which is found in the serum of patients suffering from e.g. bronchogenic, mammary, urogenital and gastrointestinal carcinomas, the beta-S-fetoprotein which is most likely to be identical with C-reactive protein, gamma-fetoprotein, the carcinofetal antigen in glial tumors (CFGA); ectopic production of placental hormones like human gonadotropin, placental lactogen, plasminogen-activators; leukemia-associated antigens. Furthermore, some other less known carcinofetal antigens are mentioned.
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PMID:[Carcinofetal antigens. III. Further carcinofetal antigens (author's transl)]. 115 52

Fetal basal ganglia astrocytes and C6 glioma cells were plated on the surface of 1.5 cm thick hydrated collagen I wafers. Both cell types migrated through the entire thickness of the wafer within 1 day after plating. The collagen in the wafer was digested and the fine collagen I fibrils were clumped into large strands. By 2-3 days, the collagen strands were digested from the wafers and replaced by a mass of fetal astrocytes or C6 cells joined by their processes. The collagen I digestion and cell migration suggested protease production. In a second series of experiments, cultured C6 cells and E14 fetal astrocytes were immunohistochemically stained for the presence of plasminogen activators as an index of protease production. Both tissue (tPA) and urokinase (uPA) types were observed. Fetal astrocytes and C6 cells were also positive for guanidinobenzoatase, a serine protease associated with migrating cells. These data demonstrate that rapid migration of the cells on and through collagen I fibrils is concomitant with expression of plasminogen activators and proteases which can either activate or function as collagenases and release the cells from the substrate.
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PMID:Mechanisms of C6 glioma cell and fetal astrocyte migration into hydrated collagen I gels. 149 72

The human [Glu1]-plasminogen carbohydrate isozymes, plasminogen type I (Pg 1) and plasminogen type II (Pg 2), were separated by chromatography and studied in cell binding experiments at 4 degrees C with primary cultures of rat hepatocytes and rat C6 glioma cells. In both cell systems, Pg 1 and Pg 2 bound to an equivalent number of receptors, apparently representing the same population of surface molecules. The affinity for Pg 2 was slightly higher. With hepatocytes, the KD for Pg 1 was 3.2 +/- 0.2 microM, and the KD for Pg 2 was 1.9 +/- 0.1 microM, as determined from Scatchard transformations of the binding isotherms. The Bmax was approximately the same for both isozymes. With C6 cells, the KD for Pg 1 was 2.2 +/- 0.1 microM vs. 1.5 +/- 0.2 microM for Pg 2. Again, the Bmax was similar with both isozymes. 125I-Pg 1 and 125I-Pg 2 were displaced from specific binding sites by either nonradiolabeled isozyme. The KI for Pg 2 was slightly lower than the KI for Pg 1 with hepatocytes (0.9 vs. 1.3 microM) and with C6 cells (0.6 vs. 1.1 microM). No displacement was detected with miniplasminogen at concentrations up to 5.0 microM. Activation of Pg 1 and Pg 2 by recombinant two-chain tissue-plasminogen activator (rt-PA) was enhanced by hepatocyte cultures. The enhancing effect was greater with Pg 2. Hepatocyte cultures did not affect the activation of miniplasminogen by rt-PA or the activation of plasminogen by streptokinase. Unlike the hepatocytes, C6 cells did not enhance the activation of plasminogen by rt-PA or streptokinase; however, plasmin generated in the presence of C6 cells reacted less readily with alpha 2-antiplasmin.
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PMID:Plasminogen carbohydrate side chains in receptor binding and enzyme activation: a study of C6 glioma cells and primary cultures of rat hepatocytes. 169 76

The purpose of this investigation was to characterize the reaction of alpha 2-antiplasmin (alpha 2AP) and alpha 2-macroglobulin (alpha 2M) with human plasmin bound to rat C6 glioma cells and human umbilical vein endothelial cells (HUVECs). Binding of plasmin (0.1 microM) to C6 cells at 4 degrees C did not cause cell detachment, decrease viability or change cell morphology. The KD and Bmax for the binding of diisopropyl phosphoryl plasmin (DIP-plasmin) to C6 cells were 0.9 microM and 2.6 x 10(6) sites/cell. The dissociation rate constants (koff) for 125I-plasmin were 9.7 x 10(-4) and 4.0 x 10(-4) s-1 at 4 degrees C in the presence and absence of 0.3 microM DIP-plasmin, respectively. Similar constants were determined for 125I-plasminogen and 125I-DIP-plasmin. Neither alpha 2AP nor alpha 2M affected the dissociation of DIP-plasmin. C6 cell-associated 125I-plasmin reacted slowly with alpha 2AP; however, the inhibition rate constants exceeded the koff. alpha 2AP-plasmin complex formed after the plasmin dissociated into solution (reaction pathway 1) and by direct reaction of alpha 2AP with cell-associated enzyme (reaction pathway 2). High concentrations of alpha 2AP favored pathway 2. C6 cell-associated plasmin was also protected from inhibition by alpha 2M. While the same pathways were probably involved in this reaction, alpha 2M was less effective than alpha 2AP as an inhibitor of nondissociated plasmin (pathway 2). When C6 cell-bound plasmin reacted with alpha 2AP, alpha 2AP-plasmin complex was recovered primarily in the medium, suggesting dissociation of complexes formed on the cell surface. Plasmin-receptor dissociation and inhibition experiments were performed at 22 degrees and 37 degrees C, confirming the conclusions of the 4 degrees C studies. Comparable results were also obtained using HUVEC cultures. These studies demonstrate that cell-associated plasmin is protected from inhibition by alpha 2M as well as alpha 2AP. At least two reaction pathways may be demonstrated for the inhibition of plasmin that is initially receptor-bound; however, neither pathway is highly effective, accounting for the "plasmin-protective" activity of the cell surface.
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PMID:Inhibition of cell surface receptor-bound plasmin by alpha 2-antiplasmin and alpha 2-macroglobulin. 171 17

Changes in the fibrinolytic and coagulation values measured preoperatively in brain tumor patients have not been done systematically using individual rather than global assays. Such measurements can provide meaningful information on the status of tumor-host interactions and could potentially help in predicting thromboembolic and hemorrhagic tendencies. A complete fibrinolytic profile including total fibrinolytic activity (TFA), tissue plasminogen activator (t-PA), plasmin inhibitor (PI), plasminogen activator inhibitor (PAI), protein C (PC) and plasminogen (PLG) was obtained preoperatively in 114 brain tumor patients. PLG and PI did not show much variation among the groups. TFA was slightly reduced (15%) in patients with malignant brain tumors. t-PA, however, was abnormally low in several patients and in almost 40% of patients with brain metastasis. PAI was above the upper limit of normal in approximately 50% of the patients but particularly in glioma, glioblastoma and metastasis patients. Finally, mean PC was abnormally increased in the glioblastoma and metastasis groups (p less than 0.001). This is the first study that has measured protein C in brain tumor patients. In conclusion, plasma fibrinolytic levels show marked changes in a substantial number of brain tumor patients prior to surgery--suggesting an ongoing tumor-host interaction.
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PMID:Plasma fibrinolytic profile in patients with brain tumors. 182 14

Expression of plasminogen activator (PA) enzyme activity is believed to be one of the mechanisms by which malignant cells cause pericellular proteolysis of stromal structures during implantation and tissue invasion. In this study, four cell lines derived from human gliomas were studied to ascertain which PA enzymes and PA inhibitors determine the level of secreted PA activity. A plasminogen-dependent esterolytic assay was used, and two lines (U251 and U373) were found to secrete high levels of PA activity, while PA activity was undetectable in the conditioned media from the remaining two lines (U138 and LM). The PA produced by U251 and U373 resolved as single bands comigrating with high molecular weight urokinase (Mr 54,000) on casein-plasminogen zymography. Northern blot analysis demonstrated high levels of mRNA for urokinase-type PA (uPA) in U251 and U373, as well as a considerably lower level of uPA message in LM. U251 and U373 also contained mRNA for tissue-type PA (tPA), although secreted tPA activity was not demonstrated by zymography. The U138 line contained essentially undetectable levels of mRNA for either uPA or tPA. U138 was also unique in secreting PA inhibitor activity and contained high levels of mRNA for PA inhibitor 2, which was not seen in any other line. All cell lines contained PA inhibitor 1 mRNA, with substantially more expression in the U138 and LM lines than in U251 and U373. None of the lines secreted measureable anti-plasmin activity. We conclude that there is considerable heterogeneity among human glioma cells in expression of PA enzymes and PA inhibitors. The coordinated regulation of these proteins likely determines secreted PA activity and the resultant role of plasminogen activation in tumor implantation and invasion.
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PMID:Expression of heterogeneous profiles of plasminogen activators and plasminogen activator inhibitors by human glioma lines. 237 61

Plasminogen activators (PAs) play an important role in normal and neoplastic neuromorphogenesis in the central nervous system. Proper function of proteinases such as PA may require focusing of activity on a cellular level. In this study, we demonstrate that highly purified plasminogen binds to receptors on rat C6 glioma cells in culture. Specific binding is reversible and saturable at 4 degrees C. The Kd is 1.95 +/- 0.31 microM and the Bmax is 3.6 x 10(6) molecules/cell. At 37 degrees C, there is no evidence for ligand digestion or internalization. Plasminogen receptors may concentrate potential proteinase near membranes of glia during normal and neoplastic development in the central nervous system.
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PMID:Expression of plasminogen receptors on C6 glioma cells. 254 75

Plasminogens were purified by affinity chromatography from bovine, ovine, porcine, canine, and rat plasma. The binding of each plasminogen to rat hepatocytes in primary culture and to rat C6 glioma cells was studied by radiodisplacement experiments. All of the plasminogens inhibited human 125I-[Glu1]plasminogen type 2 binding to specific cell surface receptors. The IC50 values were similar. These studies suggest conservation of the receptor recognition site in plasminogens across species lines.
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PMID:Binding of bovine, ovine, porcine, canine, and rat plasminogen to rat hepatocytes and rat C6 glioma cells in vitro. 255 24

Basic fibroblast growth factor (bFGF), a growth factor for many cell types including newborn rat astroglial cells, stimulates in a dose-dependent fashion the release of plasminogen activators (PAs) by these cells as measured by the fibrin-overlay method or the Coleman and Green's colorimetric assay. This effect of bFGF on PAs secretion (about 4.5-fold increase at 40 ng/ml bFGF) does not result from an aspecific stimulation of protein secretion by astrocytes and is only partly correlated with the mitogenic activity of bFGF. bFGF was also tested on two clonal glioma cell lines (C6 and LN18). Only one of those cell types (LN18) showed a stimulated PA release in the presence of bFGF. These data are discussed with respect to the putative roles of plasminogen activators in the developing nervous system.
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PMID:Brain basic fibroblast growth factor stimulates the release of plasminogen activators by newborn rat cultured astroglial cells. 318 69


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