Plasminogen activators (PAs), a family of
proteases active in blood coagulation, may play an important role in
cancer. Indeed,
blood coagulation disorders, such as altered
fibrinogen and
fibrin metabolism and increased incidence of vascular
thrombosis, are common in patients with advanced malignant disease. Different types of human
tumors are known to contain high levels of PA. The isoelectric focusing patterns of the PAs present in
tumors and plasma from patients with
breast cancer were compared with those of purified human
urokinase and
melanoma tissue PA. The pattern of isoelectric molecular forms of PA active at pH 8 showed two groups of several bands: in plasma from
tumor-bearing patients and controls, these groups were in the pl ranges of 6.6 to 6.8 and 8.0 to 8.5; in mammary
adenocarcinoma tissue, the ranges were 6.8 to 7.9 and 9.0 to 9.4. These patterns were different from those obtained with purified markers; the latter were 5.8 to 9.4 and 5.9 to 7.6 for purified human
urokinase and
melanoma plasminogen tissue activator, respectively. PA activity in
tumor-bearing patients was very high in malignant tissue and, on the contrary, very decreased in plasma; this latter decrease was correlated with the presence of
metastases in the axillary lymph nodes. These results suggest that the high PA activity in the
tumor tissue might participate in the destruction of the peritumoral tissue, thus allowing its invasion by
tumor cells, whereas the low activity of PA in the plasma might increase plasma
fibrin, reflecting thus an early disorder in blood coagulation which would enhance the formation of
metastases.