The Role of Stefin A in Breast Metastasis
Abstract
Metastatic breast cancer is a life threatening disease with limited treatment options. Molecular markers that can either predict accurately if a patient is likely to develop metastatic disease or be used as therapeutic targets are lacking. To address this, we have used a clinically relevant murine model of spontaneous metastasis to lung and bone, to identify candidate genes involved in metastatic progression. By microarray profiling and immunohistochemistry, we found enhanced expression of the cathepsin inhibitor Stefin A in epithelial cells isolated from primary tumors and their matched spontaneous metastases in lung and bone. In the human disease, patients lacking primary tumor expression of Stefin A had improved disease free survival and expression of Stefin A was enhanced in lung and bone metastases. As an endogenous inhibitor, we proposed that Stefin A is a marker of enhanced cathepsin activity in metastatic tumors. To explore this, we measured cathepsin activity using protease specific fluorescent substrates and found increased activity of cathepsin B in highly metastatic primary tumors. Stefin A and cathepsin B co-localise at the invasive fronts of primary tumors and in lung and bone metastases in the murine model and in human breast cancer. This study implicates cathepsins and their inhibitor Stefin A in breast cancer metastasis and provides evidence that Stefin A has prognostic value in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2006
- Accession Number
- ADA462586
Entities
People
- Belinda S. Parker
Organizations
- University of Melbourne