HUMAN UROKINASE RECEPTOR CONCENTRATION IN MALIGNANT AND BENIGN BREAST-TUMORS BY IN-VITRO QUANTITATIVE AUTORADIOGRAPHY - COMPARISON WITH UROKINASE LEVELS

We measured the tissue concentration or human urokinase receptor (uPAR ) in 22 breast carcinomas and 9 benign breast lesions using in vitro q uantitative autoradiography. Tissue sections were incubated with incre asing concentrations of I-125-pro-urokinase in the presence or absence of unlabeled competitor. Breast carcinomas were found to contain 5 ti mes more uPAR than benign breast lesions with respect to their protein content [523 +/- 72 versus 108 +/- 20 (SE) fmol/mg (P < 0.001)]. Simu ltaneous quantitation of urokinase (uPA) by immunoenzymatic assay on t issue extracts from the same specimens showed that breast carcinomas a lso contain 19 times more uPA than benign tumors (611 +/- 134 versus 3 2 +/- 8 fmol/mg) (P < 0.01). The reliability of quantitative autoradio graphy measurements was confirmed by uPAR cross-linking assay on membr ane fraction from either U937 histiocytic lymphoma cells or breast car cinomas and immunoperoxidase staining with an anti-uPAR antibody on tu mor sections. Also, immunoperoxidase staining with an anti-uPA monoclo nal antibody showed that uPA is indeed localized on the plasma membran e of epithelial tumor cells in confined areas of breast carcinomas whe reas cells from benign breast lesions were devoid of uPA under the sam e experimental conditions. In conclusion, our findings support the hyp othesis that uPAR plays a central role in the acquisition of an invasi ve phenotype and favor its potential use as a prognostic factor in pat ients with breast carcinoma.