Secretion of cathepsin B and tumour invasion.

Abstract

Lysosomal proteases in health and disease 1,ysosomal proteases have been implicated in a variety of pathophysiological processes, such as the malignant progression of tumours [ 11, muscular dystrophy [2], acute inflammation [3] and complications accompanying the ageing process [4]. In nonpathological situations, these proteolytic enzymes are generally found inside cells, i.e. within the endosomal/lysosomal compartment. They have a broad activity spectrum and their major role is, therefore, believed to be in the intracellular degradation of endocytosed proteins [ 51 and possibly in the processing of class I1 major histocompatibility complex (MHC)-restricted antigens [6]. Mammalian lysosomes contain many proteases, among them the cathepsins R, C, H, I, and S, which are all members of the papain family of cysteine proteases [7]. Cathepsin R has been the cysteine protease most widely studied in health and disease for two reasons. First, its trypsin-like substrate specificity made it possible to assay the enzyme with existing synthetic substrates for serine proteinases at an early stage in the studies [5]. Secondly, cathepsin R is known to be less tightly controlled by specific endogenous inhibitors, the cystatins, than other lysosomal cysteine proteases [8], making it easy to detect in tissue homogenates and complex biological fluids.