Plasminogen activators: possible roles in cell proliferation.

ABSTRACT

Plasminogen activators (PAs) convert plasminogen to plasmin by the cleavage of the Arg-Val bond. There are two distinct types of PA, tissue type (t-PA) released from the endothelial cells of the blood vessels and urinary type (u-PA) released from urinary tubules. u-PA was found to be released from activated macrophages and virally transformed cells. t-PA was also found to be released from breast cancer cells induced by carcinogens or melanoma cells. In structure, t-PA has a finger domain homologous to fibrin-binding domain of fibronectin and a growth factor domain homologous to the epidermal growth factor. u-PA has no finger domain but has a growth factor domain. It is proposed that PA may be important in tumor growth due to the stimulation of tumor cells through binding of growth factor domain to its receptor of tumor cells. Another hypothesis is that PA may activate procollagenase to collagenase, which digests collagen to facilitate tumor growth. We have measured the concentrations of t-PA and u-PA in plasma, urine and tumor tissues of patients with cancer of the digestive tract and patients with uterine or ovarian tumors. The results indicate that the concentrations of u-PA increased in urine, plasma and cancer tissues of patients with cancer of the digestive tracts whereas no increase was observed in t-PA levels. On the other hand, the concentration of t-PA increased mostly in plasma of patients with uterine and ovarian cancers, but t-PA levels in tissues did not increase in patients with uterine and ovarian cancer.