INHIBITION OF IN-VIVO TUMORIGENICITY AND INVASIVENESS OF A HUMAN GLIOBLASTOMA CELL-LINE TRANSFECTED WITH ANTISENSE UPAR VECTORS

Our previous studies showed that glioblastomas express increased uroki nase-type plasminogen activator receptors (uPARs) in comparison to low -grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994), To explore whether downregulation of uPAR inhibits tumor formation and i nvasiveness, a human globlastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5' end in an an tisense orientation, resulting in a reduced number of uPA receptors, C o-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed t o invade fetal rat brain aggregates, Intracerebral injection of SNB19- AS1 stable transfectants failed to form tumors and were negative for u PAR expression in nude mice, Thus uPAR appears in this model to be ess ential for tumorigenicity and invasion of glioblastomas in vivo.