Cathepsin B and its role(s) in cancer progression

Experimental and clinical evidence has linked Cathepsin B with tumour invasion and metastasis. Cathepsin B expression is increased in many human cancers at the mRNA, protein and activity levels. In addition, Cathepsin B is frequently overexpressed in premalignant lesions, an observation that associates this protease with local invasive stages of Cancer. Increased expression of Cathepsin B in primary cancers, and especially in preneoplastic lesions, suggests that this Enzyme might have pro-apoptotic features. Expression of Cathepsin B is regulated at many different levels, from gene amplification, use of alternative promoters, increased transcription and alternative splicing, to increased stability and translatability of transcripts. During the transition to malignancy, a change in the localization of Cathepsin B occurs, as demonstrated by the presence of Cathepsin B-containing vesicles at the cell periphery and at the basal pole of polarized cells. Due to increased expression of Cathepsin B and changes in intracellular trafficking, increased secretion of procathepsin B from tumours is observed. Active Cathepsin B is also secreted from tumours, a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface, where binding to the annexin II heterotetramer occurs. Activation of Cathepsin B on the cell surface leads to the regulation of downstream proteolytic cascade(s).