Data from Novel Role of Thromboxane Receptors β Isoform in Bladder Cancer Pathogenesis

These studies were undertaken to determine the potential role of thromboxane receptors (TP) in bladder cancer. The data reported herein show that expression of the TP-β receptor protein is increased in tissue obtained from patients with bladder cancer and associated with a significantly poorer prognosis (P < 0.005). Bladder cancer cell lines express the TP-β isoform, unlike immortalized nontransformed urothelial cells (SV-HUC) that express only the TP-α isoform. TP-β receptor expression, but not TP-α, promoted cell proliferation, migration, and invasion in vitro, and also resulted in malignant transformation of SV-HUC cells in vivo. Agonist-mediated phosphorylation of extracellular signal-regulated kinase and FAK was dependent on the expression of TP-β. Furthermore, TP-β mediated multiple biological effects by signaling through either G-protein α subunit 12 or β-arrestin 2. Treatment of mice with the TP receptor antagonist GR32191, alone or in combination with cisplatin, significantly delayed tumor onset and prolonged survival of mice transplanted with TCC-SUP bladder cancer cells compared with vehicle or cisplatin alone. These results support the model that the TP-β receptor isoform plays a unique role in bladder cancer progression and its expression may have predictive value and provide a novel therapeutic target. [Cancer Res 2008;68(11):4097–104]