Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture

Abstract

THERE is evidence that fibrinolytic enzymes are involved in the growth of tumours. It has long been known that malignant tumours in culture lyse clotted plasma substrates^1–3. Davidson et al.⁴ found a giant-cell carcinoma of the lung to be rich in plasminogen activator and to produce it in tissue culture. Rifkin et al.⁵ reported an abundant release of fibrinolytic enzymes by mammalian fibroblasts transformed by DNA or RNA viruses, by chemically or virally induced mammary carcinomas and by human malignant tumours in culture. Normal fibroblasts and cultures of other normal tissues released little or no fibrinolytic enzymes. Christman and Acs⁶ found neoplastic cells, whether transformed by oncogenic viruses or by chemical agents, to release a plasminogen activator not released by normal cells. This activator was characterised as a serine protease with a molecular weight of approximately 50,000. The presence of fibrinolytic activity has been demonstrated in human ovarian tumours⁷ as well as in ascitic fluid associated with such tumours⁸. We have studied a stable plasminogen-activating enzyme, released by ovarian carcinoma in tissue culture, and we report here the apparent identity of this plasminogen activator (TA) and the activator produced by foetal kidney and present in normal urine—that is, urokinase.