Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors.

Abstract	Our previous studies showed that glioblastomas express increased urokinase-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 invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5' end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.
Authors	Y Go, S K Chintala, S Mohanam, Z Gokaslan, B Venkaiah, R Bjerkvig, K Oka, G L Nicolson, R Sawaya, J S Rao
Journal	Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 15 Issue 4 Pg. 440-6 (Jul 1997) ISSN: 0262-0898 [Print] Netherlands
PMID	9219733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antisense Elements (Genetics) PLAUR protein, human Plaur protein, mouse Plaur protein, rat Receptors, Cell Surface Receptors, Urokinase Plasminogen Activator Recombinant Proteins beta-Galactosidase
Topics	Animals Antisense Elements (Genetics) (genetics, pharmacology) Brain (embryology, pathology) Carcinogenicity Tests Coculture Techniques Female Glioblastoma (drug therapy, genetics, pathology) Humans Mice Mice, Nude Neoplasm Invasiveness Neoplasms, Experimental (genetics) Rats Rats, Sprague-Dawley Receptors, Cell Surface (drug effects, genetics) Receptors, Urokinase Plasminogen Activator Recombinant Proteins (genetics, metabolism) Staining and Labeling Transfection Tumor Cells, Cultured beta-Galactosidase (genetics, metabolism)

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