Sphingosine-1-phosphate stimulates human glioma cell proliferation through Gi-coupled receptors: role of ERK MAP kinase and phosphatidylinositol 3-kinase beta

Cancer Lett. 2002 Jul 26;181(2):195-204. doi: 10.1016/s0304-3835(02)00050-2.


The regulation of glioma cell proliferation by sphingosine-1-phosphate (S1P) was studied using the human glioblastoma cell line U-373 MG. U-373 MG cells responded mitogenically to nanomolar concentrations of S1P, and express mRNA encoding the S1P receptors S1P1/endothelial differentiation gene (EDG)-1, S1P3/EDG-3 and S1P2/EDG-5. S1P-induced proliferation required extracellular signal-regulated kinase activation and was partially sensitive to pertussis toxin and wortmannin, indicating involvement of a Gi-coupled receptor and phosphatidylinositol 3-kinase. Moreover, S1P1, S1P3 and S1P2 receptors are expressed in the majority of human glioblastomas as determined by reverse transcriptase-polymerase chain reaction analysis. Thus, S1P signaling through EDG receptors may contribute to glioblastoma growth in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Cell Division / drug effects
  • DNA / biosynthesis
  • GTP-Binding Protein alpha Subunits, Gi-Go / physiology*
  • Glioma / pathology*
  • Humans
  • Lysophospholipids*
  • Mitogen-Activated Protein Kinases / physiology*
  • Phosphatidylinositol 3-Kinases / physiology*
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology*
  • Tumor Cells, Cultured
  • Wortmannin


  • Androstadienes
  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • sphingosine 1-phosphate
  • DNA
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Sphingosine
  • Wortmannin