Hyaluronic Acid and Hyaluronidase in Prostate Cancer: Evaluation of Their Therapeutic and Prognostic Potential
Annual rept. 1 Jan-31 Dec 2003
MIAMI UNIV FL SCHOOL OF MEDICINE
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The limited knowledge about which clinically localized prostate cancer Cap would progress, and when it will recur severely impedes individualization of therapy and prediction of outcome. Several molecules that function in cancer growth and progression can serve prognostic indicators. Treatment modalities that target the functions of these molecules could effectively control CaP progression. We have studied two such molecules hyaluronic acid HA and HYALl type hyaluronidase HAase. HA is a glycosaminoglycan and HAase is an enzyme that degrades HA into angiogenic fragments. Immunohistochemical analysis using archival radical prostatectomy CaP specimens from patients on whom theree is minimum 6-year follow-up range 72 - 131 months show that HYALl and combined HA-HYALl staining are independent predictors for biochemical recurrence. Functional analysis of HYALl by stable cDNA transfection and in vitro and in vivo studies show that both over and under production of HYALl severely inhibits CaP growth and its invasive potential. Use of 3 HAase inhibitors show that inhibition of HAase activity also inhibits CaP cell proliferation. The degree of inhibition show that inhibition of HAase activity also inhibits CaP cell proliferation. The degree of inhibition of cell proliferation is dependent on the degree of inhibition of HAase activity. Ongoing studies are examining the effect of HAase inhibition on gene expression by cDNA microarray analysis.
- Anatomy and Physiology
- Medicine and Medical Research