The differential effects on primary tumor growth and on the formation of spontaneous pulmonary metastases have been determined for a series of proteinase inhibitors. The substances included the gold compounds, aurothioglucose and aurothiomalate, D(-)penicillamine, phosphoramidon and an egg-white inhibitor of cysteine proteinase (EWI). The i.p. administration of these substances to mice bearing s.c. Lewis lung carcinoma cause varying degrees of antineoplastic effects; the most pronounced effects on metastases are caused by phosphoramidon. The inactivity of EWI on tumor progression is concomitant with an inhibition to 50% of cathepsin B in tumor homogenates. The selective antimetastatic action of phosphoramidon is in agreement with the crucial role proposed for tumor collagenases in tumor dissemination.
