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.