Stable Transfection of Urokinase-Type Plasminogen Activator Antisense Construct Modulates Invasion of Human Glioblastoma Cells

摘要: The diffuse and extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modifications proteolysis extracellular matrix components. A key molecule in regulating plasminogen-mediated urokinase-type plasminogen activator (uPA). To investigate role uPA invasive process tumors, we stably transfected a human glioblastoma cell line SNB19 with vector capable expressing an antisense transcript complementary 1020 bases at 3' end cDNA. Parental, vector-, construct-stably lines were analyzed for mRNA by Northern blot analysis, enzyme activity zymography, protein levels Western blotting. mRNA, protein, activities significantly lower clones than parental controls. Radioreceptor binding studies demonstrated that receptor remained same parental, antisense-transfected cells. cells showed markedly level invasion Matrigel assays, their spheroids failed invade fetal rat aggregates coculture system. Green fluorescent (GFP) transfectants was generated detection mouse tissue without any posttreatment. Intracerebral injection stable reduced tumor formation compared Our results suggested down-regulation expression may be feasible approach reducing malignancy invasiveness glial tumors.