HOST CATHEPSIN-D RESPONSE TO TUMOR IN THE NORMAL AND PEPSTATIN-TREATED MOUSE

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2584-2587
Abstract
In view of the postulated role of cathepsin D in cachexia, investigations were pursued on the host tissue response of cathepsin D activity in DBA/2 mice inoculated with 5 .times. 105 L1210 [leukemia] tumor cells. The results confirmed previous investigators'' findings of the increase in cathepsin D activity (specific activity) in liver and muscle of tumor bearers. This increase was a general response of the host since heart, kidney, lung and spleen cathepsin D specific activity were also enhanced in tumor bearers. These increases ranged from an average of 10% for spleen to 100% for gastrocnemius muscle. This effect was age related in heart and kidney. As a working hypothesis, the concept that tumor bearers release protease-enhancing factor(s) which trigger increase or enhancement of cathepsin D activity in host tissues by yet unknown mechanisms is proposed. Pepstatin (60 mg/kg), a known inhibitor of cathepsin D in vitro, provides long-lasting inhibition (3-6 days) of cathepsin D in vivo in non-tumor bearers particularly in spleen, liver, kidney, lung and heart. Evidence is provided from assays of cell fractions that this inhibition takes place at or in the lysosome. The duration of the effectiveness of pepstatin was altered in tumor bearers in that cathepsin D activity of heart, lung and spleen had returned to near normal values in 48 h following pepstatin injection. However, in muscle, liver and kidney, significant inhibition (90%) still persisted in tumor bearers as it did in non-tumor bearers. Pepstatin or related antiproteases may prove useful as anti-cachexia agents by decreasing proteolysis in muscle and other tissues.