Cell Surface Regulation of Matrix Metalloproteinases in Breast Cancer Cells
Abstract
Metastasis is the major cause of death in breast cancer patients and is partly caused by the action of proteolytic enzymes that degrade extracellular matrix (ECM). We have focused on the gelatinases, MMP-2 and MMP-9, two ECM-degrading enzymes that are members of the matrix metalloproteinase (MMP) family of proteases. The gelatinases are associated with the surface of breast cancer cells. MMP-2 surface binding plays a role in activation by MT1-MMP, a membrane-bound MMP that is also expressed in breast cancer. MMP-2 activation is mediated by the action of TIMP-2, a metalloproteinase inhibitor. However, the role of TIMP-2 in pro-MMP-2 activation by MT1-MMP is not clear. Although MMP-9 is identified on the cell surface, the mechanism of MMP-9 surface association and regulation remains to be investigated. The research of the Academic Award during the second year has focused on the mechanisms involved in pro-MMP-2 activation and MMP-9 surface association. We report a detailed characterization of the activation of pro-MMP-2 and the interactions of TIMP-2 and TIMP-4 with MT1-MMP during this process. We also carried phage display studies to identify MMP-9-binding proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA396418
Entities
People
- Rafael Fridman
Organizations
- Wayne State University