Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1)

The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well-differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-I) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts, The mRNA expressing cells in the in site hybridization sections were evaluated and counted by two different observers, The number of mRNA expressing cells for uPA, uPAR and PAI-I were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-I mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI-I genes in the solid tumors suggest a correlation with a more aggressive pheno type. (C) 2001 Wiley-Liss, Inc.