The Role of EMMPRIN in Tumor Progression
Abstract
Crucial steps in tumor progression and the process of metastasis, e.g. tumor growth, invasion through extracellular matrices and angiogenesis, involve proteolytic modification of the pericellular matrix surrounding tumor cells. A major class of proteases involved in these processes is the matrix metalloproteinases (MMPs), and inhibition of MMPs prevents progression and metastasis of several tumor types, including human breast carcinomas, in animal models. In vivo, tumor MMPs are usually produced by stromal cells associated with tumors rather than the tumor cells themselves. The tumor cell surface glycoprotein, EMMPRIN, stimulates MMP production by fibroblasts and endothelial cells, and may be an important regulator of MMP production during tumorigenesis in vivo. The focus of this proposal is to demonstrate directly whether or not EMMPRIN promotes breast cancer progression and whether a role for EMMPRIN in tumor progression may be to promote or induce angiogenesis. This study should determine definitively whether EMMPRIN-mediated regulation of MMPs may constitute a newly discovered step in breast carcinoma progression and metastasis. Results obtained to date indicate that increased expression of EMMPRIN leads to increased breast carcinoma growth and invasion, and supports the possibility that EMMPRIN stimulates angiogenesis. Our results also indicate that interference with EMMPRIN action may be an effective way to retard breast carcinoma progression in patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2000
- Accession Number
- ADA382507
Entities
People
- Bryan Toole
Organizations
- Tufts University