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

Human glioma cells (T98G and A172 cell lines) were cultured on various extracellular matrix (ECM) components including type I, IV and V collagens, fibronectin, laminin, and reconstituted basement membrane (Matrigel), and the role of matrix metalloproteinases (MMPs) in their growth and invasion was examined. T98G glioma cells grew well on these ECM components and invaded the reconstituted basement membrane. In contrast, A172 glioma cells showed growth inhibition on collagen types IV and V and Matrigel without invasion of the Matrigel. Gelatin zymography and enzyme immunoassays demonstrated that T98G glioma cells, but not A172 cells, secrete a large amount of matrix metalloproteinase-2 (MMP-2, 72 kD gelatinase/type IV collagenase = gelatinase A), and this was confirmed by immunoblotting and immunohistochemistry. Of the two different tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), T98G cells produced only TIMP-1 during culture on Matrigel, whereas A172 cells secreted both. Although both human recombinant TIMP-1 and TIMP-2 stimulated T98G cell growth slightly on Matrigel, the in vitro invasiveness was significantly reduced by only recombinant TIMP-2. These results suggest that MMP-2 plays an important role in the ECM invasion of T98G human glioma cells in vitro.
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PMID:Secretion of matrix metalloproteinase-2 (72 kD gelatinase/type IV collagenase = gelatinase A) by malignant human glioma cell lines: implications for the growth and cellular invasion of the extracellular matrix. 874 May 87

Since the extracellular matrix (ECM) has a role in regulating cell proliferation it has been hypothesized that unregulated growth of transformed cells results from an inability of cells to interpret the constraints on growth as dictated by the ECM. The most likely candidate to communicate the restraint on growth to the nucleus is the cytoskeleton because it is the only cytoplasmic structure to physically connect the nucleus and plasma membrane. The purpose of this study was to determine whether the cytoskeleton, specifically the microfilaments (MF), of the C6-glioma cell line possesses the ability to respond to changes in the ECM. The C6-glioma cell line was chosen as a model because it exhibits the characteristics of a tumor cell, both in vivo and in vitro. In this study cells were grown on bare glass, Matrigel, laminin and type IV collagen prior to staining with phalloidin tetramethylrhodamine B isothiocyanate or antibodies specific to vinculin to visualize MF and adhesion plaques, respectively. On the basis of MF orientation, network complexity and location of adhesion plaques, this study reports that the cytoskeletal arrangements of C6 cells grown on various substrates are distinctly different. Each distinct organization pattern may reflect a change of cell behavior promoted by the different culture conditions. The significance of this study is that it demonstrates that the process of transformation in C6-glioma cells has not interfered with the cells ability to recognize, interpret and adapt to changes in the ECM.
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PMID:Extracellular matrix regulates microfilament and vinculin organization in C6-glioma cells. 877 43

An induction of laminin in the confrontation zone between tumor cells and normal brain tissue has been observed in our model systems in vivo and in vitro. In order to study the effects of ECM components on glioma-cell migration and invasion, we have used 2 lacZ-transfected glioma cell lines, AN1/lacZ and U-251 /lacZ. Cell migration from multicellular spheroids was studied using different types of media: DMEM with 10% serum, Ultra Culture medium, and filtrated DMEM with serum in which the protein fraction > 100 kDa had been removed by ultrafiltration. Laminin, fibronectin and collagen type-IV were individually added to the different media, and cell migration from the spheroids was studied. The results show that cell migration in both cell lines, was stimulated by laminin and fibronectin. Collagen type-IV stimulated only cell migration of U-251/lacZ cells. Scanning electron microscopy revealed an extensive change in cell shape as a result of laminin stimulation. Flowcytometric studies showed that both AN1/lacZ and U-251/lacZ strongly express the alpha3 beta1 integrin receptor, which can bind to several ECM components (laminin, fibronectin, collagen). Immunofluorescence microscopy demonstrated that the same integrin sub-units were expressed in multicellular spheroids. When monoclonal antibodies to alpha3 and beta1 were added to the laminin-stimulated cultures, cell migration was significantly reduced. This indicates that the alpha3 beta1 integrin receptor plays an important role during glioma-cell migration.
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PMID:Stimulation of glioma-cell migration by laminin and inhibition by anti-alpha3 and anti-beta1 integrin antibodies. 882 48

Extracellular matrix (ECM) constituents likely play an important role in cell proliferation and the invasion of malignant human gliomas. We examined the formation of stress fibers and the growth of the human glioblastoma cell lines A172 and T98G cultured on collagen types I, IV, and V, laminin (LN), and fibronectin (FN). A172 cells cultured on LN and FN formed complete F-actin filaments after 24 h of culture and grew logarithmically after 48 h. In contrast, T98G cells on LN and FN reorganized only short F-actin filaments after 24 h of culture and grew rapidly after 72 h. However, on the collagen preparations, neither cell line formed definite stress fibers and both showed lower rates of cellular proliferation. Significantly positive correlation was observed between the relative intensity of F-actin filaments and the cell proliferation. The results indicate that the ability of ECM components to modulate the growth and differentiation of malignant glioma cells may be mediated, in part, by the assembly and disassembly of F-actin filaments.
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PMID:Organization of F-actin filaments in human glioma cell lines cultured on extracellular matrix proteins. 884 54

The invasion/migration of two cell lines, melanoma (MEW) and glioma (BT5C), and their counterparts treated for prolonged time with TPA were studied. On Western blots both cell lines expressed alpha, beta I protein kinase C isoforms, whereas beta II and gamma were not detected. The down-regulation of alpha and beta I PKC was observed in glioma cells after long treatment with TPA, whereas the same treatment of melanoma cells did not lead to PKC downregulation. The down-regulation of PKC was accompanied by stimulation of cell migration/invasion through Transwell chambers coated with collagen IV or fibronectin. In the case of melanoma cells treated with TPA, whose PKC was not down-regulated, the inhibition of migration/invasion was observed. The invasive properties of studied cells did not correlate with any conventional PKC isoform expression.
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PMID:The pleiotropic effect of TPA on in vitro invasion/migration of glioma and melanoma cell lines. 894 14

Based on in vitro studies which demonstrate that collagen IV and laminin inhibit the proliferation and invasiveness of glioma cells, we investigated the clinical significance of these extracellular matrix proteins (ECM) in patients with gangliogliomas, tumors in which ECM is often a prominent feature. Our study compared the relative presence and deposition pattern of collagen IV and laminin in 19 gangliogliomas and in 18 gliomas without ganglion cell differentiation (8 low-grade astrocytomas, 7 anaplastic astrocytomas, and 3 anaplastic mixed gliomas). We also examined whether the presence of collagen IV and laminin correlated with other features often observed in gangliogliomas, including perivascular lymphocytic inflammation, granular bodies, microcalcification, and subarachnoid extension, and whether any of these features were associated with the patient's clinical course. Significant deposition of collagen IV and laminin was found in 9 gangliogliomas (47%), but in none of the other gliomas. The presence of these extracellular proteins in gangliogliomas correlated with both perivascular inflammation (P = 0.003), and involvement of the leptomeninges by tumor (P = 0.008). The duration of symptoms prior to surgical resection was significantly longer for patients whose tumors showed extracellular deposition of collagen IV and laminin than for patients whose tumors lacked deposition of these proteins (mean 13.7 vs 5.1 years; P = 0.02). In addition, the duration of symptoms was significantly longer for patients whose tumors exhibited perivascular inflammation than for patients whose tumors displayed little or no perivascular inflammation (mean 14.8 vs 4.8 years; P = 0.01). These findings suggests that collagen IV and laminin and perivascular inflammation are related to the indolent behavior of gangliogliomas.
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PMID:The clinical significance of extracellular matrix in gangliogliomas. 895 48

The aim of this study was to evaluate the effects of various cell culture conditions on cell morphology. Cell morphology was estimated by means of video recording and computer-assisted image analysis. Cell contours from the stored images of either live cells or fixed and stained cells were determined automatically, and cellular area, form factor, and average cell brightness were calculated. Using the mouse fibroblastoid L 929 cell line (L-cells) and the rat glioma BT4C cell line, it was found that a number of methodological parameters strongly affected cell morphology. These included confluency of cells before dissociation, dissociation procedure, cell seeding density, cultivation time, and culture substratum. The substratum, particularly collagen type I and fibronectin, profoundly affected cell morphology. Using drugs affecting cytoskeletal organization or cell substratum interactions, it was shown that average cell brightness was a valuable parameter for estimation of cellular attachment. Cytochalasin D, which impairs actin filaments, caused a dramatic increase in the average cell brightness in both cell lines. Nocodazole, which depolymerizes microtubules, mainly affected the L-cells, whereas the BT4C-cells were largely unaffected, indicating that microtubules were morphological determinants for the former cell line but not for the latter. When cells were grown on fibronectin, an RGD-peptide only affected L-cell attachment, indicating that BT4C-cells only expressed low (if any) amounts of RGD recognizing integrins. The interassay precision of the employed procedure depended on culture substratum; the coefficients of variation ranged from 7-24%. Lowest variations in area determination were found for cells grown on fibronectin. The coefficient of variation of form factor determinations was generally around 20%, independent of substrata and culture time.
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PMID:Evaluation of cell morphology by video recording and computer-assisted image analysis. 901 77

Collagen IV, laminin and fibronectin are constituents of the cerebral extracellular matrix (ECM), which is critical in glioma cell invasion. The aim of the present study was to evaluate the integrin dependent cell-matrix interactions of two tumors with different invasive properties under matrixfree conditions. Two human glioma (GaMG, U373) and melanoma (MV3, BLM) cell lines were grown in serum free medium. Immunofluorescence microscopy of collagen IV, laminin, and fibronectin was performed. The adhesion of monolayer cells and their migration out of multicellular spheroids was quantified for these ECM components. Integrin chains known to act as laminin receptors were blocked by specific antibodies in additional migration assays. All cell lines expressed all the ECM components under serum free conditions. Tumor cell adhesion and migration in both glioma and melanoma cell lines was increased by all the ECM components, laminin being the strongest promotor of migration. However, migration was dose dependent in gliomas, whereas melanomas revealed a dose optimum of 10 micrograms/ml laminin. Antibodies against alpha 3 integrins significantly reduced migration on laminin in all cell lines, anti-beta 1 in all cell lines except U373. Anti-alpha 2 in BLM showed a strong effect, anti-alpha 6 was a stronger inhibitor in glioma than in melanoma cells. Integrins are functionally involved in tumor cell locomotion on laminin. The blocking of laminin related integrin chains markedly reduces cell motility in a varying manner between the cell lines. Moreover, different cell lines utilize different integrins as the laminin receptor.
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PMID:ECM dependent and integrin mediated tumor cell migration of human glioma and melanoma cell lines under serum-free conditions. 904 41

While distant metastases are rare in patients with primary brain malignancies, local growth and invasion are common and life-threatening. Regional infiltration is responsible for the failure of local therapies, resulting in tumor recurrence, progression, and death. The process of invasion requires cellular adhesion, local proteolysis and migration. CAI, carboxyamide-triazole, is an anticancer agent developed as an inhibitor of selected signal transduction pathways. Studies on the effects of CAI on human glioblastoma growth and invasiveness are presented. CAI inhibited proliferation of 6 of 8 cell lines tested in a dose-dependent fashion in vitro (IC50 range 1.5-44 microM), with no effect on the U373 line. Inhibition of adhesion to tissue culture plastic was observed for the H4, T98G, and U373 lines pretreated with CAI; H4 and T98G were inhibited in adhesion to collagen type IV. Incubation with CAI decreased production of the 72 kDa and 92 kDa type IV collagenases in all cell lines, ranging from 16 to 93% inhibition. These observations show that the effects of CAI on cell line behavior can vary between lines that are similar in origin. Despite variability in the inhibitory effects for proliferation and adhesion, CAI is consistently able to inhibit the invasive phenotype of all glioma cell lines in vitro using the Matrigel barrier assay (IC50 range 13-28 microM). These observations suggest that CAI may have benefit in the treatment of gliomas and high grade astrocytomas.
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PMID:Inhibitory effects of CAI in glioblastoma growth and invasion. 912 May 49

To analyse the interactions between glioma cells and extracellular matrix (ECM) proteins, the adhesive and migratory capacity of five human glioma cell lines (D37MG, D54MG, GaMG, U118MG and U251MG) were studied. The expression of integrins was analysed and correlated to the adhesive and migratory abilities of the cells. All cell lines were able to adhere to and migrate on the extracellular matrix proteins collagen IV, fibronectin, laminin and vitronectin. Laminin was superior in propagating adhesion and migration in all five cell lines. As analysed by flow cytometry, the expression of the integrin subunits alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, beta 3, beta 4, alpha v, and integrin alpha v beta 5 proved to be uniform between the cell lines. All integrins except alpha 4, alpha 6, beta 3 and beta 4 were expressed on more than 85% of the cells. Inhibition of adhesion with synthetic peptides and antibodies directed against integrins demonstrated that adhesion on laminin was independent of integrins and the 67 kD laminin receptor. On the other hand, migration was shown to be integrin-dependent on all substrates. The results indicate that the mechanism responsible for cell adhesion in human gliomas differ from those present during migration, and that integrins play an important role in regulating these two mechanisms.
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PMID:Adhesion and migration of human glioma cells are differently dependent on extracellular matrix molecules. 913 46


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