Novel Tissue Inhibitor of Metalloproteinase, TIMP-4, in Human Breast Cancer Growth and Metastasis
Abstract
TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and characterized. Enzymatic kinetic studies revealed IC(50) values of 19, 3, 45, 8, and 83 nM for MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9, respectively. TIMP-4 has a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we administrated TIMP-4 both locally by transfection of the gene into breast cancer cells and systemically by a gene therapy approach with intramuscular injection of TIMP-4 expression plasmid. Overexpression of TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion assay. When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA383090
Entities
People
- Yuenian Shi