Journal article

Cathepsin B inhibition limits bone metastasis in breast cancer

NP Withana, G Blum, M Sameni, C Slaney, A Anbalagan, MB Olive, BN Bidwell, L Edgington, L Wang, K Moin, BF Sloane, RL Anderson, MS Bogyo, BS Parker

Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2012

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. ..

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Grants

Awarded by National Cancer Institute


Funding Acknowledgements

This work was supported by the U.S. Department of Defense BCRP Concept Award W81XWH-05-1-0444 (B. S. Parker), National Health and Medical Research Council (NHMRC) grant 509325 (B. S. Parker, R. L. Anderson, and M. S. Bogyo) and Career Development Award 566553 (B. S. Parker), National Breast Cancer Foundation (Australia) fellowship (R. L. Anderson), NHMRC postgraduate scholarship ID 466645 (to N.P. Withana). This work was also supported, in part, by the NIH [R01CA131990 (B. F. Sloane)] and NIH/National Cancer Institute grant ROI CA90291 (R. L. Anderson).