Thromboxane Synthase and Prostate Cancer Progression

Abstract

Abstract : The initiation and progression of prostate cancer remain not well understood to enable development of interventional therapy. Thromboxane synthase is an enzyme downstream of cyclooxygenase, utilizing prostaglandin H to form thromboxane A2. Using immunohistochemistry analysis, we found that 25% of clinical prostate tumor specimens had strong expression of thromboxane synthase; 33% of cases had medium expression and 42% of cases had weak expression of thromboxane synthase. Prostate cancer cells isolated from lymph node metastasis had higher levels of thromboxane synthase expression and activity than those isolated from the primary tumor sites in an animal model. We cloned and sequenced full-length thromboxane synthase cDNA from PC-3 cells and constructed an expression vector. Increased expression of thromboxane synthase in DU145 cells was found to stimulate cell migration. Inhibition of thromboxane synthase or blockade of thromboxane A2 function inhibited prostate cancer cell migration. Further we found that PCa cells express receptors for TXA2 and stimulation with TXA2 mimetic led to the activation of RhoA and cell retraction. Our study suggest that thromboxane synthase and its eicosanoid product play a contributory role in prostate cancer progression.