The cell surface urokinase-type plasminogen activator receptor (uPAR) has been shown to be a key molecule in regulating plasminogen-mediated extracellular proteolysis. To investigate the role of uPAR in invasion of brain tumors, human glioblastoma cell line SNB19 was stably transfected with a vector capable of expressing an antisense transcript complementary to the 300 base pair of the 5' end of the uPAR mRNA. Parental and stably transfected (vector, sense, and antisense) cell lines were analysed for uPAR mRNA transcript by Northern blot analysis, and receptor protein levels were measured by radioreceptor assays and Western blotting. Signi®-cant reduction of uPAR sites was observed in the antisense transfected cell lines. The levels of uPAR mRNA were signi®cantly decreased in antisense clones compared to control, vector and sense clones. The invasive potential of the cell lines in vitro was measured by Matrigel invasion assay and migration of cells from spheroids to monolayers. The antisense transfected cells showed a markedly lower level of invasion and migration than the controls. The antisense clones were more adhesive to the ECM components compared to parental, vector and sense clones. All transfected (vector, sense and antisense) clones and parental cells produced similar levels of uPA activity without any signi®cant dierence however, MMP-2 activity was decreased in antisense clones compared to controls. These results demonstrate that uPAR expression is critical for the invasiveness of human gliomas and down regulation of uPAR expression may be a feasible approach to decrease invasiveness.
The authors present studies of eight patients who had obstruction of the superior sagittal sinus caused by parasagittal meningioma. The results indicate that meningeal veins and end-to-end anastomoses of the superficial veins of the cerebrum play important roles as collateral venous pathways. This assessment suggests that, in patients with obstruction of the superior sagittal sinus, venous phase angiography should be carefully interpreted before surgery is attempted for parasagittal meningiomas.
Primary brain tumors lack the metastatic behavior that is in part believed to be promoted by the extracellular matrix (ECM) components of the basement membrane. This study was intended to examine the influence of the ECM components present in the basement membrane that may act as natural barriers to tumor cell invasion. We examined the effect of type I and type IV collagens, fibronectin, laminin, and hyaluronic acid on the migration and invasion of four established glioblastoma cell lines, SNB19, U251, UWR1, and UWR2. Lower concentrations of all the ECM components induced the migration and invasion of all the cell lines. However, in the case of SNB19, laminin inhibited both migration and invasion in a concentration-dependent manner. We have also examined the influence of individual ECM components on the migration of cells from a spheroid to a monolayer on ECM component-coated coverslips. Consistent with the invasion studies using the modified Boyden chamber assays, lower concentrations of ECM components induced the migration of cells from spheroids to monolayer. Again, laminin inhibited the migration of cells from SNB19 spheroids. These results indicate that ECM components induce the invasion of glioma cells, apart from components like laminin, which may act as natural inhibitors.
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