Effect of Antisense Inhibition of Urokinase Receptor on Malignancy
Plasminogen activator of the urokinase type (uPA) has been shown to be overexpressed in most experimental malignant tumors and human cancers (Dano et al. 1985; DeBruin et al. 1987; Sappino et al. 1987; Markus 1988; Sim et al. 1988; Duffy et al. 1990; Janicke et al. 1990; Testa and Quigley 1990; Sappino et al. 1991; Mignatti and Rifkin 1993). The overproduction of uPA by tumor cells was detected in primary cultures, organ cultures, and cancer cell lines. However, examination by in situ analyses (both immunocytochemistry and in situ hybridization) of sections of human tumors consisting of multiple cell types identified in some instances cells other than cancer cells as the uPA producers. Depending on the type of cancer, and in some instances the laboratory and the reagents used to perform the analysis, tumor, stromal, and sometimes infiltrating macrophages were found to be the main source of uPA and/or its receptor (Grondahl-Hansen et al. 1991; Pyke et al. 1991, 1993; Bianchi et al. 1994; Carriero et al. 1994). Regardless of its source, however, it has been firmly established in several human cancers that high levels of uPA are predictive of more aggressive disease with shorter relapse-free survival (Duffy et al. 1990; Janicke et al. 1990, 1991; Grondahl-Hansen et al. 1993; Kobayashi et al. 1994).
KeywordsChick Embryo Urokinase Receptor Antisense Inhibition uPAR Expression uPAR mRNA
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- Behrfendt N, Ploug M, Patthy L, Houen G, Blasi F, Dano K (1991) The ligand binding domain of the cell surface receptor for urokinase-type plasminogen activator. J Biol Chem 266: 7842–7847Google Scholar
- DeBruin PA, Griffioen G, Verspaget HV, Verheijen JH (1987) Plasminogen activators and tumor development in the human colon. Activity levels in normal mucosa, adenomateous tissue, polyps and adenocarcinomas. Cancer Res 47: 4654–4657Google Scholar
- Grondahl-Hansen J, Christensen IJ, Rosenquist C, Brunner N, Mouridsen HT, Dano K, Blichert-Toft M (1993) High levels of urokinase-type palsminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Res 53: 2513–2521PubMedGoogle Scholar
- Lu H, Yeh P, Guitton JD, Mabilat C, Desanlis F, Maury I, Legrand Y, Soria J, Soria C (1994) Blockage of the urokinase receptor on the cell surface: construction and characterization of hybrid protein consisting of the N-terminal fragment of human urokinase and human albumin. FEBS Lett 356: 56–59PubMedCrossRefGoogle Scholar
- Ossowski L, Russo-Payne H, Gartner M, Wilson EL (1987) Inhibition of urokinase-type plasminogen activator by antibodies: the effect of dissemination of human tumor in the nude mouse. Cancer Res 51: 274–281Google Scholar