A link between malignancy and impaired haemostatic function has been suggested for some time. However, the clinical implication remains confused and mutually exclusive hypotheses concerning the nature of this link are in vogue. This report concerns part of a study designed to establish the nature of this association and to define whether it is causal or accidental.Initial experiments indicated that there was no clear correlation between malignancy, transformation and plasminogen activator (PA). Indeed, cultures of the malignant cell lines Hela and Hep2 and of a transformed lung fibroblast line produced little PA while two normal lines, MRC 5 and WI38 produced very high amounts of PA. In vivo data were obtained from human breast tumours which had been classified into those which contained steroid binding receptors and those which did not. PA levels were measured in tumour extracts by means of two assays, a functional 125I-labelled fibrin digestion technique and a radioimmunometric method. Enzymic activity was also screened on a range of synthetic chromogenic substrates.PA levels were consistently lower in those breast tumours containing steroid receptors, the ratio of PA activity in receptor-negative and receptor-positive tumours ranging from 1.43 to 3.03. All samples contained small amounts of antiplasmin-like activity and some contained other haemostatic component activities including thrombin, kallikrein and Factor Xa.Our results do not confirm the findings of other workers who have demonstrated a positive correlation between breast tumour plasminogen activator activity and the level of steroid receptors. Plasminogen activator levels may thus be of limited prognostic value in determining the hormoneresponsiveness of breast tumours and cast doubt on the view that malignant cells produce increased amounts of PA.
