23 research outputs found
Novel bi- and trifunctional inhibitors of tumor-associated proteolytic systems
Serine proteases, cysteine proteases, and matrix metalloproteinases (MMPs) are involved in cancer cell invasion and metastasis. Recently, a recombinant bifunctional inhibitor (chCysuPA(19-31)) directed against cysteine proteases and the urokinasetype plasminogen activator (uPA)/plasmin serine protease system was generated by introducing the uPA receptor (uPAR)binding site of uPA into chicken cystatin (chCysWT). In the present study, we designed and recombinantly produced multifunctional inhibitors also targeting MMPs. The inhibitors comprise the Nterminal inhibitory domain of human TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) or TIMP-3, fused to chCysuPA(19-31) or chCysWT. As demonstrated by various techniques, these fusion proteins effectively interfere with all three targeted protease systems. In in vitro Matrigel invasion assays, the addition of recombinant inhibitors strongly reduced invasion of ovarian cancer cells (OVMZ-6\#8). Additionally, OVMZ 6\#8 cells were stably transfected with expression plasmids encoding the various inhibitors. Synthesis and secretion of the inhibitors was verified by a newly developed ELISA, which selectively detects the recombinant proteins. Invasive capacity of inhibitorproducing cells was significantly reduced compared to vectortransfected control cells. Thus, these novel, compact, and smallsize inhibitors directed against up to three different tumorassociated proteolytic systems may represent promising agents for prevention of tumor cell migration and metastasis
Differential role of cathepsins B and L in autophagy-associated cell death induced by arsenic trioxide in U87 human glioblastoma cells
Comparison of Expression of Cathepsins B and L and MMP2 in Endothelial Cells and in Capillary Sprouting in Collagen Gel
Identification of cysteine protease inhibitors that belong to cystatin family 1 in the cellular slime mold Dictyostelium discoideum
Clinical and Experimental Studies of Cysteine Cathepsins and Their Inhibitors in Human Brain Tumors
Wild type p53-dependent transcriptional upregulation of cathepsin L expression is mediated by C/EBPα in human glioblastoma cells
Cathepsins B and L and Their Inhibitors Stefin B and Cystatin C as Markers for Malignant Progression of Benign Meningiomas
Implications pronostiques de différents marqueurs biologiques dans les méningiomes intracrâniens : à propos de 120 cas
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