Endometase in Androgen-Repressed Human Prostate Cancer
Abstract
The spread of prostate cancer cells to other parts of the body is the leading cause of patient death. In 2000, we reported the discovery, cloning, and characterization of human matrix metalloproteinase-26 (MMP-26), endometase. We have been testing three specific hypotheses: 1) The expression levels of MMP-26 is correlated with the metastatic potentials and the degrees of malignancy of human prostate cells; 2) MMP-26 has unique structure and enzymatic function; 3) MMP-26 enhances prostate cancer invasion by digesting extracellular matrix proteins and inactivating serine proteinase inhibitors, and specific inhibitors of MMP-26 block prostate cancer invasion. We have showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. Human breast carcinoma in situ also expressed high levels of MMP-26 protein. Prostate cancer cells transfected with MMP-26 cDNA are more invasive than the parental cell lines. MMP-26 promoted prostate cancer invasion via activation of progelatinase B/MMP-9. The endometase active site structure has been revealed to have an intermediate Sl' pocket using synthetic metalloproteinase inhibitors. Endometases may be a novel marker for prostate cancer detection and a new target for therapy. Reprints published by Sang lab are attached.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA425166
Entities
People
- Qing-xiang A. Sang
Organizations
- Florida State University