Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Cathepsin B Inhibition Limits Bone Metastasis in Breast Cancer CANCER RESEARCH Withana, N. P., Blum, G., Sameni, M., Slaney, C., Anbalagan, A., Olive, M. B., Bidwell, B. N., Edgington, L., Wang, L., Moin, K., Sloane, B. F., Anderson, R. L., Bogyo, M. S., Parker, B. S. 2012; 72 (5): 1199-1209

    Abstract:

    Metastasis to bone is a major cause of morbidity in breast cancer patients, emphasizing the importance of identifying molecular drivers of bone metastasis for new therapeutic targets. The endogenous cysteine cathepsin inhibitor stefin A is a suppressor of breast cancer metastasis to bone that is coexpressed with cathepsin B in bone metastases. In this study, we used the immunocompetent 4T1.2 model of breast cancer which exhibits spontaneous bone metastasis to evaluate the function and therapeutic targeting potential of cathepsin B in this setting of advanced disease. Cathepsin B abundancy in the model mimicked human disease, both at the level of primary tumors and matched spinal metastases. RNA interference-mediated knockdown of cathepsin B in tumor cells reduced collagen I degradation in vitro and bone metastasis in vivo. Similarly, intraperitoneal administration of the highly selective cathepsin B inhibitor CA-074 reduced metastasis in tumor-bearing animals, a reduction that was not reproduced by the broad spectrum cysteine cathepsin inhibitor JPM-OEt. Notably, metastasis suppression by CA-074 was maintained in a late treatment setting, pointing to a role in metastatic outgrowth. Together, our findings established a prometastatic role for cathepsin B in distant metastasis and illustrated the therapeutic benefits of its selective inhibition in vivo.

    View details for DOI 10.1158/0008-5472.CAN-11-2759

    View details for Web of Science ID 000300989100019

    View details for PubMedID 22266111

Stanford Medicine Resources:

Footer Links: