抄録
Background: Plasma-derived lipid mediator sphingosine-1-phosphate (S1P) acts via the G protein-coupled S1P receptor family to regulate a variety of physiological and pathological responses. S1P1 receptor mediates endothelial cell migration and vascular maturation, promoting vascular integrity. We have previously shown that S1P2R is distinct from S1P1R in that it negatively regulates cell migration and endothelial capillary tube formation in vitro. In the present study we investigated the role of S1P2R in tumor angiogenesis by using S1P2 knock out (KO) mice. Methods and Results: Lewis lung carcinoma cells were injected into the flank of S1P2KO and wild type (WT) mice and allowed to grow for 14 days. Tumors in S1P2KO mice displayed increased numbers of blood vessels, which were associated with much higher numbers of desmin-positive mural cells, and marked upregulation of angiogenic factors including VEGF and the Notch signaling mediator Delta-like ligand 4. Vascular permeability examined by FITC-dextran administration was decreased in S1P2KO compared with WT mice. Conclusions: S1P2R negatively regulates tumor angiogenesis in vivo, with inhibition of angiogenic gene expression, mural cell recruitment and vascular integrity. S1P2R-selective agonist would be a promising candidate for anti-tumor angiogenesis. [J Physiol Sci. 2008;58 Suppl:S52]
