Endometase in Androgen-Repressed Human Prostate Cancer
Abstract
Prostate cancer invasion and metastasis is the leading cause of patient death. 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 report that levels of MMP-26 protein in human prostate carcinomas and high-grade prostate intraepithelial neoplasia from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. Prostate cancer cells transfected with MMP-26 cDNA are more invasive and with an inactive mutant are less invasive than the parental cell lines. MMP-26 promoted prostate cancer invasion via activation of pro-gelatinase B/MMP-9. The endometase active site has an intermediate S1' pocket using synthetic MMP inhibitors. Some new synthetic MMP inhibitors are stable in cell culture media and can block the invasion of prostate cancer cells. Papers published by Sang lab are attached.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437246
Entities
People
- Qing-xiang A. Sang
Organizations
- Florida State University