A novel role for the urokinase-type plasminogen activator receptor in apoptosis of malignant gliomas.
Glioblastomas express more urokinase-type plasminogen activator receptor (uPAR) than do low-grade gliomas and normal brain tissue. We previously showed that downregulation of uPAR through the transfection of SNB19 cells with an antisense cDNA construct corresponding to 300 bp of the 5' end of the human uPAR gene inhibited tumor cell invasion in vitro and tumor formation in vivo. Here we sought to determine whether uPAR is necessary for cell survival and whether the inhibition of tumor formation in nude mice is due to apoptosis of intracerebrally injected SNB19 cells. Apoptosis measured by DNA fragmentation were higher in the brains of animals injected with the antisense stable transfectants than in those injected with the parental cells. Moreover, the increase in apoptotic cell death in vitro was associated with increased expression of apoptotic protein BAX in antisense clones compared to controls. To our knowledge, this is the first report of uPAR playing a novel role in cell survival in human gliomas.
Kin
Y
Y
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Chintala
S K
SK
Go
Y
Y
Sawaya
R
R
Mohanam
S
S
Kyritsis
A P
AP
Rao
J S
JS
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology* / Q000517:prevention & control; D016373:DNA, Antisense / Q000494:pharmacology; D005260:Female; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010960:Plasminogen Activators / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators