Dual functionality of phosphonic-acid-appended phthalocyanines: inhibitors of urokinase plasminogen activator and anticancer photodynamic agents

2015 ◽  
Vol 51 (85) ◽  
pp. 15550-15553 ◽  
Author(s):  
N. Venkatramaiah ◽  
Patrícia M. R. Pereira ◽  
Filipe A. Almeida Paz ◽  
Carlos A. F. Ribeiro ◽  
Rosa Fernandes ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Plasminogen Activator ◽  
Phosphonic Acid ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Bladder Cancer Cells ◽  
Phosphonic Acid Groups ◽  
Metalloproteinase 9

Phthalocyanines with phosphonic acid groups have a PDT effect on UM-UC-3 bladder cancer cells and inhibit urokinase-type plasminogen activator and matrix metalloproteinase-9.

scholarly journals Regulation of proteinases during mouse peri-implantation development: urokinase-type plasminogen activator expression and cross talk with matrix metalloproteinase 9

Reproduction ◽  
2011 ◽  
Vol 141 (2) ◽  
pp. 227-239 ◽  
Author(s):  
M G Martínez-Hernández ◽  
L A Baiza-Gutman ◽  
A Castillo-Trápala ◽  
D Randall Armant
Keyword(s):  
Matrix Metalloproteinase ◽  
Mrna Expression ◽  
Plasminogen Activator ◽  
Type Iv Collagen ◽  
Matrix Metalloproteinase 9 ◽  
Trophoblast Cells ◽  
Type Iv ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Metalloproteinase 9

Trophoblast cells express urokinase-type plasminogen activator (PLAU) and may depend on its activity for endometrial invasion and tissue remodeling during peri-implantation development. However, the developmental regulation, tissue distribution, and function of PLAU are not completely understood. In this study, the expression of PLAU and its regulation by extracellular matrix proteins was examined by RT-PCR, immunocytochemistry, and plasminogen–casein zymography in cultured mouse embryos. There was a progressive increase inPlaumRNA expression in blastocysts cultured on gestation days 4–8. Tissue-type plasminogen activator (55 kDa) and PLAU (a triplet of 40, 37, and 31 kDa) were present in conditioned medium and embryo lysates, and were adsorbed to the culture plate surface. The temporal expression pattern of PLAU, according to semi-quantitative gel zymography, was similar in non-adhering embryos and embryos cultured on fibronectin, laminin, or type IV collagen, although type IV collagen and laminin upregulatedPlaumRNA expression. Immunofluorescence revealed PLAU on the surface of the mural trophectoderm and in non-spreading giant trophoblast cells. Exogenous human plasminogen was transformed to plasmin by cultured embryos and activated endogenous matrix metalloproteinase 9 (MMP9). Indeed, the developmental expression profile of MMP9 was similar to that of PLAU. Our data suggest that the intrinsic developmental program predominantly regulates PLAU expression during implantation, and that PLAU could be responsible for activation of MMP9, leading to localized matrix proteolysis as trophoblast invasion commences.

scholarly journals 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

2005 ◽  
Vol 280 (23) ◽  
pp. 21882-21892 ◽  
Author(s):  
Sajani S. Lakka ◽  
Christopher S. Gondi ◽  
Dzung H. Dinh ◽  
William C. Olivero ◽  
Meena Gujrati ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumor Growth ◽  
Plasminogen Activator ◽  
Tumor Invasion ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Antisense Approach ◽  
Plasminogen Activator Receptor ◽  
Metalloproteinase 9

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.

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