On the prevention of haematogenous tumor metastases rats. The role of the proteinase inhibitor "Trasylol".

All malignant tumors shed cells into the circulation. The number of circulating tumor cells bears no relation to the extent of secondary growth. This is determined by the number of tumor cells that cross the vessel wall and implant in extravascular sites. The rate of cellular emigration is regulated by the permeability of vessels harbouring tumor emboli, permeability in turn being dependent on the amount of alpha, 2, macro-globulin (AMG) lining vascular endothelium. Agents which inactivate or digest AMG, e.g. proteases, have been shown to promote the dissemination of tumor. Some tumors secrete large amounts of proteases. These enzymes are believed to lyse the AMG layer and so to facilitate the emigration of tumor cells. On this hypothesis, inhibitors of such proteases would have anti-metastatic properties. Present experiments lend support to this view. The proteinase inhibitor Trasylol, when allowed to act on tumor cells, has been shown to impair their capacity of setting up haematogenous metastases. It does not affect their viability or transplantability. It is suggested therefore, that blood-borne tumor dissemination might be inhibited by perfusing the (primary) tumor bed with proteinase inhibitor, possibly in association with AMG.