COORDINATE EXPRESSION OF URINARY-TYPE PLASMINOGEN-ACTIVATOR AND ITS RECEPTOR ACCOMPANIES MALIGNANT TRANSFORMATION OF THE OVARIAN SURFACE EPITHELIUM

OBJECTIVE: Because elevated expression and cell surface association of urinary-type plasminogen activator have been linked to invasive poten tial in certain tumor types, we examined the expression of urinary-typ e plasminogen activator and urinary-type plasminogen activator recepto r in ovarian epithelial carcinoma tissues and cells as compared with n ormal ovarian epithelium. STUDY DESIGN: Monoclonal antibodies specific for urinary-type plasminogen activator and urinary-type plasminogen r eceptor were used for immunohistochemical staining of tissues and cell s to assess expression of these antigens in frozen sections of normal and tumor tissue. Substrate zymography was used to detect plasminogen activator activity in ovarian carcinoma ascites and in conditioned med ia of cultured cells, whereas a Western blot assay was used to identif y urinary-type plasminogen activator receptor in cultured cells. RESUL TS: Normal ovarian epithelium expressed urinary-type plasminogen activ ator receptor (4/4 positive) but little or no urinary-type plasminogen activator (0/4 positive), whereas epithelial ovarian carcinomas frequ ently expressed urinary-type plasminogen activator (4/8 positive) in c onjunction with urinary-type plasminogen activator receptor (7/9 posit ive). High levels of urinary-type plasminogen activator were detected in 15 of 19 samples of ascites. DOV 13, OVCA 420, OVCA 429, OVCA 432, and OVCA 433 cell lines secreted urinary-type plasminogen activator in variable quantities, whereas normal ovarian epithelial cells did not secrete any detectable plasminogen activator. Urinary-type plasminogen activator receptor had similar levels of expression in all cancer cel l lines and normal ovarian epithelium. CONCLUSION: Overexpression of u rinary-type plasminogen activator is associated with malignant transfo rmation of the ovarian epithelium. Increased cell surface proteolysis mediated by urinary-type plasminogen activator bound to cell surface u rinary-type plasminogen activator receptor may contribute to metastati c behaviour in ovarian carcinoma.