Hyaluronan Biosynthesis in Prostate Carcinoma
Abstract
Despite advances in the diagnosis and treatment of prostate cancer in the last several years, metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA) is polymeric anionic carbohydrate that is elevated within primary prostate tumors, most notably within the tumor-associated stroma. Our studies have demonstrated that increased HA synthesis by human prostate carcinoma cells correlates with metastatic potential. This increased synthesis results from the elevated expression of specific hyaluronan synthases (HAS) in the tumor cells. Metastatic prostate carcinoma cells exhibiting high levels of HAS assemble and retain a pericellular HA matrix on their cell surfaces. These cells also exhibit selective adhesion to bone marrow endothelial cell lines in vitro, suggesting that carcinoma associated HA may enhance entry of prostate tumor cells into the bone marrow microenvironment by engaging specific receptors on the surface of these endothelial cells. Furthermore, elevated HA synthesis enhances tumor growth and vascularization in vivo following subcutaneous injection. We have used vectors to stably express constructs encoding antisense for HAS enzymes to study the importance of elevated hyaluronan synthesis in prostate carcinoma adhesion, growth and tumor formation. The studies outlined in this annual report document our observations that support an important role for hyaluronan in prostate tumor growth, progression and metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA415957
Entities
People
- James B. Mccarthy
Organizations
- University of Minnesota