Hyaluronan Synthesis and Turnover in Prostate Cancer

Several genetic susceptibility loci have been identified that may account for higher risk through reduced ability to cope with environmental insults. Tumors detected early are often managed effectively by surgical resection and/or hormone ablation therapy. However, a significant percentage of tumors will resume growth in the absence of androgens. This chapter provides an understanding of the transformation from androgen dependent to androgen independent prostate cancer. It also discusses the clinical correlation and functional roles of hyaluronan (HA) synthases, hyaluronidases, and HA receptors in specific aspects of prostate cancer. Relatively few genetic determinants of prostate cancer have been identified and the well documented role of inflammation in prostate carcinogenesis is addressed. Synthesis and deposition of HA is normally associated with cell division, motility, transformation, and vascular development in embryogenesis. Many studies have demonstrated the strong correlation between HA accumulation and malignancy in solid tumors. HA production in cultured tumor cells is significantly stimulated by growth factors and proinflammatory cytokines are known to be elevated in human prostate cancer specimens. Various studies suggest an important link between clinically relevant tumor proliferation signals and inappropriate HA biosynthesis.