Cathepsin L in metastatic bone disease: therapeutic implications

Cathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests this endopeptidase may be also implicated in the regulation of other important biological functions including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodelling processes, may contribute to facilitate bone metastasis formation. In support of this hypothesis, recent studies indicate that cathepsin L may foster this process by triggering multiple mechanisms which, in part, differ from those of the major cysteine proteinase of osteoclast, namely cathepsin K. Therefore, cathepsin L may be regarded as an additional target in the treatment of patients with metastatic bone disease. This review discusses the clinical and therapeutic implications related to these findings.