Role of Proteases in Breast Cancer Progression
Abstract
Metastasis is the major cause of death in breast cancer patients. To metastasize, breast cancer cells must degrade extracellular matrices (ECM) using specialized ECM-degrading proteases including matrix metalloproteinases (MMPs) and cathepsins. The purpose of these studies was to understand the mechanisms regulating the expression, cellular localization and activation of MMP-2, MMP-9 and cathepsin B in breast epithelial and fibroblast cells. We have found that breast cancer cells can be induced to express latent MMP-9 (pro-MMP-9) by interactions with platelets and exposure to growth factors and phorbol ester. Induction of pro-MMP-9 expression results in the localization of a "IMP-free enzyme on the cell surface, a process that is partly mediated by the alpha 2(IV) chain of collagen IV. We have found that pro-MMP-2 is activated by MTl-MMP on the surface of breast fibroblasts seeded in a collagen I matrix by inducing MT 1-MMP expression. Binding of MMP-2 to the cell surface of breast cancer cells is dependent on cell density. We showed that MMP-2 could in turn activate surface-bound pro-MMP-9. Studies with cathepsin B showed a specific localization of enzyme on the surface of breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA359193
Entities
People
- Rafael Fridman
Organizations
- Wayne State University