Low levels of endostatin in the urine from patients with malignant disease

Abstract

Endostatin, a C-terminal subfragment of collagen XVIII, and angiostatin, a family of fragments originating from the NH(2)-terminal portion of plasminogen, have been described as potent inhibitors of angiogenesis and malignant growth. We have earlier reported the presence of angiostatin fragments in urine from cancer patients. In this study, we investigated the occurrence of endostatin and the correlation between the amounts of endostatin and angiostatin in urine collected from 104 patients with different types of malignancies and in 16 controls. The amounts of endostatin were measured with a commercial immunoassay. Angiostatin fragments were quantitated by Western blot analysis. Only small amounts of endostatin were observed, both in patients and controls, and there was no significant difference in the amount of endostatin between the patients and the controls. Both endostatin and angiostatin concentrations in the urine showed a strong dependence on impaired kidney function, especially tubulus function, measured as the amount of urine alpha(1)-microglobulin. Interestingly, there was no significant correlation between endostatin and angiostatin concentrations in the patients with impaired kidney function (elevated urine albumin or urine alpha(1)-microglobulin), suggesting a possible difference in circulating concentrations of these inhibitors.