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 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.
Go
Y
Y
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Chintala
S K
SK
Mohanam
S
S
Gokaslan
Z
Z
Venkaiah
B
B
Bjerkvig
R
R
Oka
K
K
Nicolson
G L
GL
Sawaya
R
R
Rao
J S
JS
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics / Q000494:pharmacology*; D001921:Brain / Q000196:embryology / Q000473:pathology; D015197:Carcinogenicity Tests; D018920:Coculture Techniques; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D016375:Antisense Elements (Genetics); C524898:PLAUR protein, human; C524899:Plaur protein, mouse; C524900:Plaur protein, rat; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D001616:beta-Galactosidase