Obesity and Cathepsin K: A Complex Pathophysiological Relationship in Breast Cancer Metastases

Breast cancer appears in a strong inclination to metastasize in bone tissue. Several strategies are discussed in combating bone metastasis in breast cancer. However, therapy is only palliative and does not provide any improvement in survival to the majority of patients with advanced cancer. Obese and overweight women with breast cancer are three times more likely to develop metastatic disease compared to normal-weight women with the same treatment regimen. Overweight greatly intensify adipocytes formation in the bone marrow affecting bone metabolism by decreasing osteoblast differentiation and bone formation. Cathepsin K (CTSK), a cysteine protease, effectively degrades several components of the extracellular matrix and has the ability to differentiate adipocytes from bone marrow lineage. Therefore, the purpose of this review is to emphasize the underlying mechanism of CTSK and obesity role in breast cancer metastasis.

Systematic review was performed using PubMed, EMBASE. The evidence of obesity and CTSK in breast cancer skeletal metastasis were analyzed, summarized and compared.

The present investigation argues for a specific association of CTSK with breast cancer skeletal metastasis by promoting adipocyte differentiation. The potential tumor-supporting roles of adipocytes are well documented, and in fact, suppressing adipocyte could be a new therapeutic option in the battle against lethal metastatic breast cancers.

This review emphasizes CTSK through its multifaceted role in differentiating adipocytes, inflammation, and extracellular degradation, may be a critical factor in an obesity-cancer connection. Thus, integration of CTSK targeting strategies into established traditional therapies seems to hold substantial promise.