Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth.
The urokinase-type plasminogen activator (uPA) and uPA receptor (UPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. sc. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established so U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.
Mohan
P M
PM
Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Chintala
S K
SK
Mohanam
S
S
Gladson
C L
CL
Kim
E S
ES
Gokaslan
Z L
ZL
Lakka
S S
SS
Roth
J A
JA
Fang
B
B
Sawaya
R
R
Kyritsis
A P
AP
Rao
J S
JS
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D016373:DNA, Antisense / Q000235:genetics*; D018450:Disease Progression; D015316:Genetic Therapy; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D009368:Neoplasm Transplantation; D009940:Organoids; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D009363:Neoplasm Proteins; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; C524900:Plaur protein, rat; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator