Cancer

Download Cancer metastatis, molecular and cellular mechanisms and by Wen G Jiang; R E Mansel PDF

By Wen G Jiang; R E Mansel

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Identification of the urokinase receptor as an adhesion receptor for vitronectin. J Biol Chem 1994; 269: 32380–32388. Yebra M, Goretzki L, Pfeifer M, Mueller BM. Urokinase-type plasminogen activator binding to its receptor stimulates tumor cell migration by enhancing integrin-mediated signal transduction. Exp Cell Res 1999; 250: 231–240. Yu HR, Schultz RM. Relationship between secreted urokinase plasminogen activator activity and metastatic potential in murine B16 cells transfected with human urokinase sense and antisense genes.

Furthermore in a variety of systems MMP-2 and 9 expression can be seen coincident with tumor progression, invasion or metastasis in naturally occurring carcinomas (Ara et al, 2000; Arenas-Huertero et al, 1999; Arii et al, 1996; Cox et al, 2000; Davidson et al, 1999; Etoh et al, 2000; Rao et al, 1996; Talvensaari-Mattila et al, 1999). These data further implicate these gelatinases in the development of aggressive malignancy. Various data implicates both of these MMPs in the processes of metastasis and angiogenesis.

Moreover, endothelial cells from PAI-1deficient hosts failed to migrate and to vascularize the implanted. As malignant PDVA cells produced uPA, tPA and PAI-1, the genotypic effect on tumor invasion and vascularization was attributable to PAI-1 produced by host 30 mesenchymal cells and/or sprouting endothelial cells. Obviously, PAI-1 produced by the cancer cells was not sufficient to overcome the host cell deficiency. This conclusion was further strengthened by the finding that the tumor invasion and vascularisation in PAI-1–/– mice were both restored by systemic adenoviral PAI-1 gene transfer (Bajou et al, 1998).

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