Aprotinin and angiogenesis in experimental oncogenesis

Background. Many investigations have demonstrated that proteolytic enzymes are implicated in tumor growth, while protease inhibitors may induce some anti-tumor effects. Besides, proteolysis is known to be involved in tumor angiogenesis. The present research examines the influence of a protease inhibitor (aprotinin) on the induction and growth of MCA-sarcoma in rats. Methods. Two experimental models were devised to assess aprotinin effects on MCA-induced sarcoma in rats. The first experiment evaluated the effects of aprotinin injections (20,000 KIU/kg b.d.) on the spot of MCA inoculation, related to the onset and the progression of sarcoma. The second experiment examined the influence of aprotinin on syngeneic grafts of MCA-sarcoma. Results. At the end of the first experiment, the differences between the control and test groups, in terms of tumor onset and animal survival, were not statistical significant. Nevertheless, in the treated group tumor growth was faster, and histology showed more necrotic tumor than those in control rats. In the second experiment, the local action of aprotinin resulted in involution of the tumor graft. Conclusions. Studies on the role of proteases in tumorigenesis have also reported some opposing effects of protease inhibitors. These indications have been clarified by recent research on tumor angiogenesis, where proteolysis is involved in mechanisms inducing angiogenic and angiostatic factors.