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- W1603801699 abstract "Plasminogen activator inhibitor type 2 (PAI-2) is one of the inhibitors of the plasminogen activation cascade mediated by urokinase (uPA) which is overexpressed on the surface of metastatic cancer cells. The plasminogen activation cascade is the generator of plasmin proteolytic activity on the cell surface which is required under normal physiological conditions and is largely exploited during cancer invasion and metastasis. The overall aim of this thesis was mainly to characterise the inhibition of cell-surface uPA by exogenously added PAI-2 and the elucidation of the fate of uPA:PAI-2 complexes once formed on the cell surface. PAI-2 was directly confirmed as a potent and rapid inhibitor of cell-surface uPA and specifically targets this antigen. PAI-2 internalised rapidly in a uPA-dependent manner after complex formation with cell-surface receptor (uPAR)-bound uPA. Internalised PAI-2 localised in endosomes/ lysosomes where it was presumably degraded. While the majority of uPAR/uPA:PAI-2 complexes formed on the cell surface were internalised, cellsurface uPA appeared to be replenished and uPAR was recycled to the cell surface. These findings were significant as they provide new information regarding cell-surface regulation of the plasminogen activation system as well as a biological rationale for the use of PAI-2 as a delivery vehicle of cytotoxins for anti-uPA therapeutic strategies. To extend the analyses of PAI-2 binding to cells and its subsequent fate, breast cancer cells were genetically modified to provide material for this study. Modulation of uPA-receptor (uPAR) expression was found to induce changes in" @default.
- W1603801699 created "2016-06-24" @default.
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- W1603801699 date "2004-01-01" @default.
- W1603801699 modified "2023-09-28" @default.
- W1603801699 title "Binding and fate of plasminogen activator inhibitor type-2 in breast carcinoma cells: rationale for development as a delivery vehicle of cytotoxins for anti-urokinase therapeutic strategies" @default.
- W1603801699 hasPublicationYear "2004" @default.
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