Downregulation of urokinase-type plasminogen activator receptor (uPAR) induces caspase-mediated cell death in human glioblastoma cells.
Urokinase-type plasminogen activator receptors (uPARs) play an important role in tumor invasion by localizing degradative enzymes at the invasive zone. Our previous studies with human glioblastoma cell line SNB19 expressing AS-uPAR stable tranfectant lose their invasive properties when injected in vivo. The aim of the present study is to investigate whether the inhibition of tumor formation is due to apoptosis. Apoptosis is a highly conserved cell suicide program essential for development and tissue homeostasis of all metazoan organisms. Key to the apoptotic program is a family of cystein proteases termed caspases, which are important for execution of apoptosis by cleavage of essential cellular proteins. We found loss of mitochondrial transmembrane potential, release of cytochrome C from mitochondria and subsequent activation of Caspase-9 in SNB 19 AS-uPAR cells compared to parental and vector controls. Our results indicate that suppression of uPAR results in apoptosis and suggest that Caspase-9 dependent apoptosis plays an important role in SNB19 AS-uPAR-induced apoptosis.
Yanamandra
N
N
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, 61605, USA.
Konduri
S D
SD
Mohanam
S
S
Dinh
D H
DH
Olivero
W C
WC
Gujrati
M
M
Nicolson
G L
GL
Obeyeseke
M
M
Rao
J S
JS
D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D020169:Caspases / Q000502:physiology*; D015536:Down-Regulation; D004789:Enzyme Activation; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D020169:Caspases