Hyaluronic Acid and Hyaluronidase in Prostate Cancer: Evaluation of Their Therapeutic and Prognostic Potential

摘要

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 as 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 HYALI 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 there is minimum 5-year follow-up, show that HYALI and combined HA-HYALI staining are independent predictors for biochemical recurrence. Patients with high HA-HYALI staining in their CaP tissues have an 18-fold increased risk of biochemical recurrence within 5-years, regardless of other clinical and pathologic parameters. Studies on functional analysis of HYALI using 3 HAase inhibitors 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 (i.e., using antisense cDNA transfection or HAase inhibitors) on CaP growth and progression in vivo.