The Role of Cathepsins in the Growth of Primary and Secondary Neoplasia in the Bone

Abstract

The upregulation of proteolytic enzymes has been demonstrated to promote primary tumor development and metastatic bone cancer. The secreted proteases increase tumor growth and angiogenesis, and potentiate neoplastic cell dissemination. This article reviews the role and mechanisms of cathepsins in normal physiology, cancer, bone remodeling, and the tumor–bone interface, with a specific focus on cathepsins B, D, H, G, L, and K. In this review, we highlight the role of cathepsins in primary bone cancer (i.e., osteosarcoma (OS)), as well as metastatic breast (BCa) and prostate (PCa) cancer. In addition, we discuss the clinical utility and therapeutic potential of cathepsin-targeted treatments in primary and secondary bone cancers.

Key Matrix Remodeling Enzymes: Functions and Targeting in Cancer

“…The cathepsin family of lysosomal proteases is a super-family of proteolytic enzymes with 15 members to date. Cathepsins are usually classified into cysteine (B, C, F, H, K, L, O, S, V, Z/X and W), serine (A and G) and aspartic (D and E) proteases, depending on the catalytic site residue and can be further subdivided in endo-peptidases (S, K, V, F, L) and both endo and exo-peptidases (B, C, H, Z/X), based on their proteolytic activity [ 173 , 174 ].…”

Anti-Periodontitis Effect of Ethanol Extracts of Alpinia Katsumadai Seeds

“…Kallikrein is involved in bone resorption by the kallikrein–kinin system and the coagulation cascade [ 31 ]. Cathepsins play roles in lysosomal protein turnover, which contributes to a plethora of physiological processes, such as antigen presentation, bone remodeling, and epidermal homeostasis [ 32 ]. The induction of MMP-2 and MMP-3 in osteoblasts is essential for bone resorption [ 33 ].…”