The purpose of this project is to investigate the relationship between tumor interaction with the fibrinolytic system and tumor metastasis. Pilot data has demonstrated a correlation between fibrinolytic activation and inhibition with respect to the presence or absence of tumor metastasis. It appears that changes in fibrinolytic activity may form the basis for a biologic marker with respect to the presence or absence of metastatic disease. Our initial assay techniques involved the use of fibrin plates for quantitation of activation and inhibition of fibrinolysis. At the present time we are in the process of revising and refining our techniques so that we may both shorten the time required for assay as well as standardize the assay. An ancillary part of the project is development of a reproducible biologic animal tumor model where we may further investigate the role of activators and inhibitors of firbinolysis with respect to tumor metastasis. Preliminary work suggests that the inhibitory fragment which we are measuring in tumors is a small molecular weight protein. This chemical agent is extractable from tumor cells and is remarkably stable over long periods of time. Very preliminary information suggests that this agent is antiplasmin or antiplasminogen. The final part of the project involves the correlation of tumor fibrinolytic data with clotting complications observed in patients whom we have studied. Although the literature documents both hyper and hypocoagulability for patients with tumors, the exact etiology of the hypercoagulable syndrome seen with metastatic disease is in a large part unknown. Our preliminary data suggests that the fibrinolytic system may be involved in the pathogenesis of thrombosis of arterial and venous segments in patients with tumors.