Novel Tissue Inhibitor of Metalloproteinase, TIMP-4, in Human Breast Cancer Growth and Metastasis
Abstract
We recently identified, cloned, and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4. The expression and biological relevance of TIMP-4 on breast cancer progression were studied. TIMP-4 was primarily expressed in the stromal fibroblasts in the mammary gland. However, the TIMP-4 protein was detected in the mammary epithelial cells with an increased level in the malignant infiltrating breast epithelial cells compared with normal breast epithelial cells. Overexpression of TIMP-4 inhibited the invasion potential of human breast cancer 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. Purified recombinant TIMP-4 protein demonstrated a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. These results suggest the therapeutic potential of TIMP-4 in treating cancer malignant progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA366514
Entities
People
- Yuenian E. Shi