Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Cell Division / drug effects
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DNA / biosynthesis
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GTP-Binding Protein alpha Subunits, Gi-Go / physiology*
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Glioma / pathology*
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Humans
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Lysophospholipids*
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Mitogen-Activated Protein Kinases / physiology*
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Phosphatidylinositol 3-Kinases / physiology*
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Receptors, Cell Surface / analysis
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Receptors, Cell Surface / physiology*
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Receptors, G-Protein-Coupled*
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Receptors, Lysophospholipid
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Sphingosine / analogs & derivatives*
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Sphingosine / pharmacology*
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Tumor Cells, Cultured
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Wortmannin
Substances
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Androstadienes
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Lysophospholipids
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, Lysophospholipid
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sphingosine 1-phosphate
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DNA
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Phosphatidylinositol 3-Kinases
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Mitogen-Activated Protein Kinases
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GTP-Binding Protein alpha Subunits, Gi-Go
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Sphingosine
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Wortmannin