HIGH TISSUE CONTENT OF UROKINASE PLASMINOGEN-ACTIVATOR (U-PA) IS ASSOCIATED WITH HIGH STROMAL EXPRESSION OF U-PA MESSENGER-RNA IN POORLY DIFFERENTIATED SEROUS OVARIAN-CARCINOMA

Urokinase plasminogen activator (u-PA) plays a pivotal role in tissue degradation during tumor spread and metastasis. We have quantitated u- PA in tissue homogenates of 31 serous ovarian tumors and localized u-P A and its mRNA in tissue sections of 26 serous ovarian tumors. The con tent of u-PA was higher in malignant than in benign tumors, with the h ighest levels being found in poorly differentiated cancers. In tissue sections, the u-PA mRNA was hybridized with a radiolabeled RNA probe. Signals were almost exclusively found in the epithelium in benign and borderline tumors and in well-differentiated cancers. Poorly different iated tumors and metastases exhibited prominent stromal expression of u-PA mRNA, whereas epithelial expression was weak or absent. Immuno-hi stochemical staining co-localized u-PA antigen with its mRNA in the ep ithelium of benign and borderline tumors and in well-differentiated ca ncers. Poorly differentiated malignant tumors showed extensive immunos taining in the epithelium in addition to stromal staining. The u-PA mR NA-expressing and u-PA-immunostained cells in the stroma were not tumo r cells since no cells in the stroma were positive for cytokeratin. Po orly differentiated tumors had increased numbers of stromal macrophage s (CD68), and they co-localized with some of the u-PA-positive cells. The presence of u-PA antigen and the absence of u-PA mRNA in tumor epi thelium of poorly differentiated tumors and metastases together with t he presence of u-PA mRNA in the stroma suggests production in stromal cells and subsequent binding to receptor sites in tumor cells. (C) 199 8 Wiley-Liss, Inc.