Role of Proteases in Breast Cancer Progression.
Abstract
Metastasis is the major cause of death in breast cancer patients. Metastasis formation depends on the ability of the tumor cells to degrade extracellular matrices (ECM) using specialized proteinases including matrix metalloproteinases (MMPs) and cathepsins. We have studied the role of tumor- stroma interactions and extracellular matrix in the expression, regulation and cell surface localization of MMP-2, MMP-9 and MTi-MMP, three members of the MMP family, and cathepsins in breast epithelial and fibroblast cells. We report on the association of latent MMP-9 to the surface of breast epithelial cells and show that the pro-a2(IV) chain of collagen Iv specifically mediates binding of the enzyme to the cell surface. The importance of the stroma in regulation of MMP and cathepsins expression was addressed using fibroblasts isolated from breast tumors cultured in collagen I gels. These studies demonstrated that culture of breast fibroblasts on collagen I induces proMMP-2 activation. Here we report some of the biochemical and molecular mechanisms involved in the collagen I-induced proMMP-2 activation and the role of MTi-MMP and TIMP-2 in this process. We have also examined the expression of cathepsins B and D in breast fibroblasts grown on collagen I.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA332670
Entities
People
- Rafael Fridman
Organizations
- Wayne State University