Hyaluronan Tumor Cell Interactions in Prostate Cancer Growth and Survival
Final rept. 25 Nov 2005-28 Nov 2009
MINNESOTA UNIV MINNEAPOLIS
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Hyaluronan is a high molecular weight polyanionic polysaccharide that is increased in more advanced prostate cancers. Tumor cell interaction with this polysaccharide by specific receptors CD44 and RHAMM promote tumor growth, survival and invasion. Work during the last funding period have further defined the mechanism of action of each of these receptors. Studies show that extracellular RHAMM acts a co-receptor for CD44, and the combined action of this receptor complex leads to sustained activation of the ERK 1,2 signal transduction pathway leading to enhance motility and produce patterns of gene transcription that are associated with invasion. Synthetic peptides have also been identified that can bind hyaluronan and inhibit the binding of this polysaccharide to its cognate receptors. These peptides inhibit tumor growth both in vitro and in vivo and the residues important for the activity of the peptides are being defined using nuclear magnetic resonance NMR. Small molecule libraries that contain compounds which may mimic these peptides are also being interrogated for the ability to inhibit hyaluronan binding to RHAMM and CD44 and to inhibit tumor growth. The goal is to develop new therapeutic strategies for patients with invasive prostate cancer.
- Anatomy and Physiology
- Medicine and Medical Research