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Title: Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P{sub 2} on cell migration and invasiveness

Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P{sub 1-5}. S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P{sub 1}, S1P{sub 2} and S1P{sub 3} all contribute positively to S1P-stimulated glioma cell proliferation, with S1P{sub 1} being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P{sub 5} blocks glioma cell proliferation, and inhibits ERK activation. S1P{sub 1} and S1P{sub 3} enhance glioma cell migration and invasion. S1P{sub 2} inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P{sub 2} also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P{sub 2}-stimulated glioma invasion. Thus, while S1P{sub 2} decreasesmore » glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix.« less
Authors:
 [1] ;  [2]
  1. Integrated Biomedical Science Graduate Program, Ohio State University, Columbus, OH 43210 (United States)
  2. Division of Neuropathology, Department of Pathology, Ohio State University, 4164 Graves Hall, 333 W. 10th Ave., Columbus, OH 43210 (United States). E-mail: james.vanbrocklyn@osumc.edu
Publication Date:
OSTI Identifier:
20972146
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 8; Other Information: DOI: 10.1016/j.yexcr.2007.02.009; PII: S0014-4827(07)00073-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIBODIES; CELL PROLIFERATION; GLIOMAS; GTP-ASES; PHOSPHATES; RECEPTORS; RNA; TUMOR CELLS