Hyaluronan Tumor Cell Interactions in Prostate Cancer Growth and Survival
Annual rept. 29 Nov 2005-28 Nov 2006
MINNESOTA UNIV MINNEAPOLIS
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Despite advances in the diagnosis and treatment of prostate cancer, the inability to inhibit metastasis represents the major cause of failure in the successful treatment of prostate cancer patients. Hyaluronan HA, a polymeric anionic polysaccharide, is elevated within primary prostate tumors and in the circulation of prostate cancer patients, and this increase is prognostic of poor outcome. Preliminary data demonstrate that HA mediates its effects on tumor cell growth and survival by interacting with two distinct cellular receptors for HA, CD44 and Rhamm CD168. CD44 and Rhamm share common functional characteristics, such as an ability to bind HA and to activate the ErkMAPK signal transduction pathway, which is associated with prostate tumor progression. We hypothesize that the HA receptor Rhamm can facilitate tumor growth, invasion and metastasis by compensating for CD44 lossreduction, particularly when the amount of HA ligand is increased, as is found in high-grade tumors. Determining the mechanisms by which pericellular HA stimulates prostate tumor growth and metastasis may lead to better therapeutics that can be used to limit the disease, allowing for the better clinical management of patients with advanced prostate cancer.
- Anatomy and Physiology
- Medicine and Medical Research