Dora Cavallo-Medved, Ph.D.
(519) 253-3000 Ext: 4750
The breast cancer microenvironment is composed of breast cancer cells and normal stromal cells (e.g. endothelial cells, fibroblasts, macrophages, etc.) that interact with each other using chemical and molecular signals. The interactions between these cells have been shown to propagate cancer growth and invasion. One mechanism is through the production and secretion of extracellular matrix degrading enzymes termed proteases. Our main research interest is focused on the role of two proteases, cathepsin B and urokinase plasminogen activator, in breast cancer progression and invasion. Given that proteases are produced and secreted by both cancer and stromal cells, we have developed 3 dimensional co-culture cell models that mimic the tumor microenvironment to better understand the basic tumour:stromal biology of breast cancer. These models can be used in conjunction with live-cell imaging to examine the functional role of these proteases in the breast cancer microenvironment. In these models, breast cancer cells form 3D spheroidal structures that become larger and more invasive when stromal cells are introduced. These aggressive characteristics are correlated with an increase in production and activity of proteases and can be repressed with the addition of protease inhibitors. Our long term objectives are to elucidate the molecular mechanisms that are regulating protease expression and activity within the breast cancer microenvironment in an effort to identify novel therapeutic strategies against the disease.
Five Most Recent Publications:
- Victor, B.C., Anbalagan, A., Mohamed, M.M., Sloane, B.F., Cavallo-Medved, D. (2011) Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion. Breast Cancer Res. 13:R115.
- Cavallo-Medved, D., Moin, K. and Sloane, B.F. (2011) Cathepsin B. UCSD Nature Molecule Pages.http://www.signalinggateway.org/molecule/query?afcsid=A000508 (doi:10.1038/mp.a000508.01) Online peer-reviewed publication
- Nouh, M.A., Mohamed, M.M., El-Shinawi, M., Shaalan, M.A., Cavallo-Medved, D., Khaled, H.M., Sloane, B.F. (2011) Cathepsin B: a potential prognostic marker for inflammatory breast cancer. J. Transl. Med. 9: 1-8
- Mohamed, M.M., Cavallo-Medved, D., Rudy, D., Anbalagan, S., Moin, K. and Sloane, B.F. (2010) Interleukin-6 increases expression and secretion of cathepsin B by breast tumor associated monocytes. Cell Physiol. Biochem. 25: 315-324.
- Cavallo-Medved, D., Rudy, D., and Sloane, B.F. (2009) Live-cell imaging demonstrates that proteases in caveolae of endothelial cells degrade extracellular matrix. Exp. Cell Res. 315: 1234-1246