Evidence for metal inhibition of tumour membrane-bound neutral protease and the control of tumour-induced target cell cytolysis.
Previous studies have characterized the enzymatic properties and inhibition of a trypsin-like neutral protease on the surface of Ehrlich ascites cells by means of kinetic analysis. The present study links these kinetic studies with the recently reported role of a tumour-cell membrane-bound serine protease in tumour-induced target cell lysis. Low-mol.-wt inhibitors of this cell-surface trypsin-like neutral protease exhibited a corresponding ability to prevent tumour-induced haemolysis. High-mol.-wt inhibitors of trypsin in free solution had no inhibitory action either on the tumour-bound enzyme or on the ability of tumour cells to lyse erythrocytes. Fragments of tumour-cell membrane retain both the trypsin-like neutral protease activity and the ability for haemolysis. This study represents a correlation between an easily assayed membrane-bound enzyme on tumour cells and a function of possible biological relevance.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D006046:Gold / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D051379:Mice; D011480:Protease Inhibitors; D013431:Sulfates / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*; D019287:Zinc Sulfate
D000893:Anti-Inflammatory Agents; D011480:Protease Inhibitors; D013431:Sulfates; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold; D019287:Zinc Sulfate; D007611:Aprotinin; D015032:Zinc