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Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas


, : Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas. Journal of Biological Chemistry 280(23): 21882-21892

We have previously demonstrated the effectiveness of adenovirus-mediated expression of antisense urokinase-type plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) in inhibiting tumor invasion in vitro and ex vivo. However, the therapeutic effect of the adenovirus-mediated antisense approach was shown to be transient and required potentially toxic, high viral doses. In contrast, RNA interference (RNAi)-mediated gene targeting may be superior to the traditional antisense approach, because the target mRNA is completely degraded and the molar ratio of siRNA required to degrade the target mRNA is very low. Here, we have examined the siRNA-mediated target RNA degradation of uPAR and MMP-9 in human glioma cell lines. Using RNAi directed toward uPAR and MMP-9, we achieved specific inhibition of uPAR and MMP-9. This bicistronic construct (pUM) inhibited the formation of capillary-like structures in both in vitro and in vivo models of angiogenesis. We demonstrated that blocking the expression of these genes results in significant inhibition of glioma tumor invasion in Matrigel and spheroid invasion assay models. RNAi for uPAR and MMP-9 inhibited cell proliferation, and significantly reduced the levels of phosphorylated forms of MAPK, ERK, and AKT signaling pathway molecules when compared with parental and empty vector/scrambled vector-transfected SNB19 cells. Furthermore, using RNAi to simultaneously target two proteases resulted in total regression of pre-established intracerebral tumor growth. Our results provide evidence that the use of hairpin siRNA expression vectors for uPAR and MMP-9 may provide an effective tool for cancer therapy.

US$19.90

PMID: 15824107

DOI: 10.1074/jbc.M408520200


Other references

B.L.nn G.W.; Ana C.A.S.; Morawski S.G.; Fordtran J.S., 1982: Effect of catharsis on caloric loses in stool measured by bomb calorimetry. Clinical Research 30(2): 555A

Mayer, J.M., 2011: A Simple Marcus-Theory Type Model for Hydrogen Atom Transfer/Proton-Coupled Electron Transfer. Hydrogen atom transfer reactions are the simplest class of proton-coupled electron transfer (PCET) processes. These reactions involve transfer of one electron and one proton from one reagent to another, in the same kinetic step: XH + Y → X + HY....

Owen, G., 1953: Studies on the phosphate problem in Malayan soils. The nature and distr. of the various forms of phosphate in soils, before and after treatment with phosphatic fertilizers, was studied in an inquiry on the causes of immobilization of the phosphate in local soils and to consider the factors respons...

Hidalgo, M.; Aponte, J.; Ramos, P.; Liprandi, F., 1999: Detection of cross-reactive antibodies in pigs vaccinated against porcine rotavirus strain OSU. Serum and colostrum samples were collected from a total of 22 sows. Ten had been vaccinated approximately 6 weeks and 2 weeks before parturition with an experimental vaccine containing the OSU strain with serotype P9 for VP4 and serotype G5 for VP...

Fischel, R., 1965: Diseases affecting the oral cavity observed in Costa Rica and Central America. In these areas of Central America, 90.8% of the school children examined showed some degree of periodontal disease. While calculus deposits were not significant, all children had mucinous plaques on their teeth. An increasing number of malignant t...

Li, H.; Clay, R.T.; Mazumdar, S., 2011: Theory of carrier concentration-dependent electronic behavior in layered cobaltates. A natural explanation for the carrier concentration-dependent electronic behavior in the layered cobaltates emerges within correlated-electron Hamiltonians with finite on-site and significant nearest neighbor hole-hole Coulomb repulsions. The near...

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L.G.; L.S.; L.B.; Fan L.; L.H., 1990: Chromosomal aberration of abnormal human oocytes and embryos in ivf et program. Among a total of 128 oocytes recovered in IVF-ET program from May 1987 to Feb. 1988, 47 failed in fertilization or abnormal cleavage were prepared for chromosomal numeration using Tarkowski's technique. Of 47 preparations, 19 revealed chromos...

Tannen, R.L., 1971: The response of normal subjects to the short ammonium chloride test: the modifying influence of renal ammonia production. Clinical Science 41(6): 583-595

Cooper A.F.; Reay A., 1983: Lithology, field relationships, and structure of the Pounamu Ultramafics from the Whitcombe and Hokitika rivers, Westland, New Zealand. The Pounamu Ultramafics comprise a series of parallel or en echelon lenses and layers of ultramafic and mafic rocks defining a northeast-striking, 2 km wide zone (the Pounamu Ultramafic Belt-PUB) in garnet zone Haast Schists of North Westland. In...