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.