Adenovirus-mediated expression of antisense urokinase plasminogen activator receptor and antisense cathepsin B inhibits tumor growth, invasion, and angiogenesis in gliomas.
Cancer Res
; 64(12): 4069-77, 2004 Jun 15.
Article
in En
| MEDLINE
| ID: mdl-15205313
ABSTRACT
We have shown previously that urokinase plasminogen activator receptor (uPAR) and cathepsin B are overexpressed during glioma progression, particularly at the leading edge of the tumor. In the present study, we simultaneously down-regulated uPAR and cathepsin B in SNB19 glioma cell monolayer or SNB19 spheroids using an adenoviral vector carrying antisense uPAR and antisense cathepsin B and a combination of these genes as determined by Western blot analysis. The Ad-uPAR-Cath B-infected cells revealed a marked reduction in tumor growth and invasiveness as compared with the parental and vector controls. In vitro and in vivo angiogenic assays demonstrated inhibition of capillary-like structure formation and microvessel formation after Ad-uPAR-Cath B infection of SNB19 cells when compared with Ad-cytomegalovirus (CMV)-infected or mock-infected controls. Furthermore, using a near infrared fluorescence probe, in vivo imaging for cathepsin B indicated low/undetectable levels of fluorescence after injection of the Ad-uPAR-Cath B construct into pre-established s.c. tumors as compared with Ad-CMV-treated and untreated tumors. The effect with bicistronic construct (Ad-uPAR-Cath B) was much higher than with single (Ad-uPAR/Ad-Cath B) constructs. These results indicate that the down-regulation of cathepsin B and uPAR plays a significant role in inhibiting tumor growth, invasion, and angiogenesis. Hence, the targeting of these two proteases may be a potential therapy for brain tumors and other cancers.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cathepsin B
/
DNA, Antisense
/
Glioblastoma
/
Receptors, Cell Surface
/
Neovascularization, Pathologic
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cancer Res
Year:
2004
Document type:
Article
Affiliation country:
United States