Primary tumor growth and formation of spontaneous lung metastases in mice bearing Lewis carcinoma treated with proteinase inhibitors.

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.