Endothelial sphingosine 1-phosphate receptors promote vascular normalization and antitumor therapy
Andréane Cartier, Tani Leigh, Catherine H. Liu, Timothy Hla
Abstract
Significance Tumor progression is dependent on angiogenesis, which supplies nutrients and enables gas exchange and metastatic dissemination. However, tumor vessels are dysfunctional and immature, which hinders the effectiveness of various therapeutics. Sphingosine 1-phosphate receptors in endothelial cells are essential for developmental angiogenesis and physiological functions such as the maintenance of the vascular barrier and vascular tone. This study shows that endothelial sphingosine 1-phosphate receptors determine the tumor vascular phenotype and maturation and that function of S1P receptor-1 is needed for tumor vascular normalization, which allows better blood circulation and enhances antitumor therapeutic efficacy in mouse models.