Mfsd2b, a Novel Sphingosine-1-Phosphate Transporter: Implication in Cancer Therapeutics

Abstract

Sphingosine-1-Phosphate (S1P) is a potent sphingolipid metabolite that regulates physiological functions including cell proliferation, survival, migration, angiogenesis, lymphocyte trafficking, mitochondrial functions as well as carcinogenesis [1]. Growing evidences suggest that S1P promotes tumor growth while inhibiting apoptosis and conferring chemoand radiation resistance to cancer cells [2]. S1P is secreted in the extracellular environment and mediates its actions by binding to a family of G-protein-coupled receptors known as S1P receptors (S1PRs) in an autocrine as well as paracrine fashion [1]. S1P concentration is more in the circulatory fluid (blood and lymph) compared to lymphoid organs and tissue interstitial fluid. In blood, most of the plasma S1P is transported in bound state to highdensity lipoprotein (HDL) and albumin. On HDL, S1P remains attached to Apolipoprotein M (Apo M) where latter may protect S1P from degradation and facilitates its presentation to receptors [3]. The major sources of plasma S1P are endothelial cells, platelets and RBCs, while lymphatic S1P is produced by lymphatic endothelial cells [3].