S1P3

Astrocytic sphingosine-1 phosphate receptor 3 (S1P3) is upregulated in the neuroinflammatory response of the highly permeable lesions, and is expressed in patients' brain metastases. S1P3 inhibition functionally tightens the BTB in vitro and in vivo. S1P3 mediates its effects on BTB permeability through astrocytic secretion of IL-6 and CCL2, which relaxes endothelial cell adhesion. Tumor cell overexpression of S1P3 mimics this pathway, enhancing IL-6 and CCL-2 production and elevating BTB permeability. In conclusion, neuroinflammatory astrocytic S1P3 modulates BTB permeability 1).

1)
Gril B, Paranjape AN, Woditschka S, Hua E, Dolan EL, Hanson J, Wu X, Kloc W, Izycka-Swieszewska E, Duchnowska R, Pęksa R, Biernat W, Jassem J, Nayyar N, Brastianos PK, Hall OM, Peer CJ, Figg WD, Pauly GT, Robinson C, Difilippantonio S, Bialecki E, Metellus P, Schneider JP, Steeg PS. Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases. Nat Commun. 2018 Jul 13;9(1):2705. doi: 10.1038/s41467-018-05030-w. PubMed PMID: 30006619.