ENDOTHELIAL AND MACROPHAGE UP-REGULATION OF UROKINASE RECEPTOR EXPRESSION IN HUMAN RENAL-CELL CARCINOMA

The binding of urokinase-type plasminogen activator (u-PA) to a specif ic cell surface receptor (uPA-R) has been shown to enhance plasminogen activation, a process involved in extracellular matrix degradation an d cell migration during angiogenesis and tumor growth. We investigated the expression of u-PA and uPA-R in renal cell carcinomas (n = 11). B y immunohistochemistry using monoclonal and polyclonal anti-uPA-R anti bodies, we found that tumoral capillary endothelial cells (von Willebr and factor and CD31 positive cells) overexpressed uPA-R, whereas vascu lar endothelial cells of the normal human kidney do not. In addition, tumor-associated macrophages (CD68-positive cells) strongly expressed uPA-R. In contrast, few tumoral cells and stromal fibroblasts expresse d uPA-R. By in situ hybridization using a cDNA S-35-labeled probe spec ific for uPA-R, we confirmed the local expression of uPA-R messenger R NA. We also detected the induction of u-PA in tumoral capillary endoth elial cells and in tumor-associated macrophages. In two cases, tumoral cells themselves were also stained by anti-u-PA antibodies in focal a reas. Finally tissue-type plasminogen activator (t-PA) was also overex pressed by tumoral capillary endothelial cells as compared with endoth elial cells of normal human kidney vessels. These findings indicate an active invasive phenotype of endothelial cells in renal cell carcinom a and suggest a role for the plasminogen activation system in tumoral angiogenesis and invasion. Copyright (C) 1997 by W.B. Saunders Company .