The Role of EMMPRIN in Tumor Angiogenesis and Metastasis
Abstract
A critical step in tumorigenesis is proteolytic modification of the peri-cellular matrix surrounding tumor cells by matrix metalloproteinases (MMPs). Stromal cells associated with tumors, not the tumor cells themselves, are responsible for the production of most tumor MMPs. Studies from our laboratory and those of our collaborators have shown that EMMPRIN (extracellular matrix metalloproteinase inducer), a tumor cell surface glycoprotein, stimulates the production of several MMPs by fibroblasts and endothelial cells. Antisense cDNA and ribozyme constructs were utilized in an attempt to inhibit EMMPRIN expression in TA3/ST cells, a murine breast carcinoma cell line. These constructs were not efficient in blocking EMMPRIN expression and consequently, were inactive in vivo. However, transfection and injection experiments done in collaboration with Dr. Stanley Zucker have shown that MDA-MB-436 human breast cancer cells transfected with GFP-EMMPRIN can produce much larger tumors in nude mice than vector-transfected cells. Also, EMMPRIN can stimulate the production of MMPs 1, 2 and 3 by endothelial cells; MMPs 1, 2 and 9 have been shown previously to promote angiogenesis. Therefore, we proposed that a possible explanation of the increased tumor growth obtained with EMMPRIN-transfected cells is an efficient nutrient supply resulting from angiogenesis. To assay whether EMMPRIN is capable of inducing angiogenesis, we treated HUVECs on type I collagen with either EMMPRIN or bFGF, a known angiogenic factor. As opposed to controls which maintained their cobblestone-like monolayer arrangement, treated HUVECs formed capillary-like tubules, lending Support to EMMPRIN as an angiogenic factor.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2000
- Accession Number
- ADA382545
Entities
People
- Bryan Toole
- Erica Mariab
Organizations
- Tufts University