MODULATION OF IN-VITRO INVASION OF HUMAN GLIOBLASTOMA CELLS BY UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR ANTIBODY

Four human glioblastoma cell lines (U251, UWR1, UWR2, and UWR3) were t ested for the expression of the cell surface receptor for urokinase-ty pe plasminogen activator (uPA). To our knowledge there have been no pr evious reports about the uPA receptors (uPARs) in glioblastoma cell li nes. All four glioblastoma cell lines we tested were found to bind rec ombinant Pro-uPA saturably and reversibly. Scatchard analysis of radio ligand binding with acid-pretreated cells showed the presence of a sin gle population of high-affinity uPARs on glioblastoma cells. Northern blot analysis confirmed that glioblastoma cells like other human cell lines express a 1.4-kilobase uPAR mRNA and 2.4-kilobase uPA mRNA. The significance of the uPAR in the invasive potential of the cells was ex amined by incubating uPAR antibody in an in vitro invasion assay. The anti-uPAR monoclonal antibody blocked the invasion effectively in a Ma trigel assay, in which inhibition of invasion ranged between 20 and 57 % for the cells studied. These data suggest that the uPARs contribute significantly to the invasive capacity of the cells, possibly by facil itating uPA activity.