title: Cathepsin B: multiple roles in cancer.
abstract: Proteases, including intracellular proteases, play roles at many different stages of malignant progression. Our focus here is cathepsin B, a lysosomal cysteine cathepsin. High levels of cathepsin B are found in a wide variety of human cancers, levels that often induce secretion and association of cathepsin B with the tumor cell membrane. In experimental models, such as transgenic models of murine pancreatic and mammary carcinomas, causal roles for cathepsin B have been demonstrated in initiation, growth/tumor cell proliferation, angiogenesis, invasion, and metastasis. Tumor growth in transgenic models is promoted by cathepsin B in tumor-associated cells, for example, tumor-associated macrophages, as well as in tumor cells. In transgenic models, the absence of cathepsin B has been associated with enhanced apoptosis, yet cathepsin B also has been shown to contribute to apoptosis. Cathepsin B is part of a proteolytic pathway identified in xenograft models of human glioma; targeting only cathepsin B in these tumors is less effective than targeting cathepsin B in combination with other proteases or protease receptors. Understanding the mechanisms responsible for increased expression of cathepsin B in tumors and association of cathepsin B with tumor cell membranes is needed to determine whether targeting cathepsin B could be of therapeutic benefit.
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Aggarwal
authors.forename: Bonnie F
authors.initials: BF
authors.lastname: Sloane
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics
chemical_list: D002401:Cathepsin B
keywords: Cancer; Cathepsin B; Cysteine proteases