Cathepsin B: Multiple roles in cancer

Authors

  • Neha Aggarwal,

    1. Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
    Search for more papers by this author
  • Bonnie F. Sloane

    Corresponding author
    1. Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA
    • Correspondence: Dr. Bonnie F. Sloane, Department of Pharmacology, Wayne State University School of Medicine, 540 E. Canfield St, Detroit, MI 48201

      E-mail: bsloane@med.wayne.edu

      Fax: +1-313–577–6739

    Search for more papers by this author

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.

Ancillary