Hyaluronic Acid as a Target for Intervention in Prostate Cancer Metastases

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Abstract : Bone metastases are a debilitating and devastating complication for patients with advanced prostate cancer. Unfortunately, treatment options for patients with bone metastases are limited. Both hyaluronan synthase (HAS) and hyaluronic acid (HA) are upregulated in metastatic prostate cancer cells. 7-Hydroxy-4-Methyl Coumarin (HMC) is an inhibitor of hyaluronan synthase. It is commonly available in herbal supplements and, up to now, has been utilized mainly for digestion complaints. We propose that it may be efficacious in the prevention and treatment of prostate cancer. Our hypothesis is that hyaluronic acid (HA) is utilized by prostate cancer cells to facilitate metastasis. Thus, reducing the production of HA should reduce the metastatic potential of prostate cancer cells making HA an ideal target for preventing and treating metastatic disease. The goal of this current research proposal is to determine whether reduction of HAS, via treatment with HMC, will prevent prostate cancer metastasis to bone and other organs or serve as a viable treatment for established prostate cancer bone metastasis. To date, we have in vivo evidence that HA protein levels in vitro correlate with metastatic potential and that HA levels can be modulated in vitro using HMC. Furthermore, we have shown the in vitro growth of prostate cancer cells is slowed by inhibition of HA with HMC.

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