The importance of β-AR-CXCR4-CXCL12 signaling as a key mediator of hemangiosarcoma progression is corroborated further by the identification of the spingosine-1-phosphate (S1P)/spingosine-1-phosphate receptor 1 (S1P1) [85] and the urokinase-type plasminogen activator (uPA)/urokinase-type plasminogen activator receptor (uPAR) [86] signaling axes within these tumors. The gene discussed is PLAU; the disease is angiosarcoma.