Document Detail

S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells.
MedLine Citation:
PMID:  18645009     Owner:  NLM     Status:  MEDLINE    
Epithelial ovarian cancer (EOC) arises from the epithelial layer covering the surface of ovaries and i.p. metastasis is commonly observed at diagnosis. Sphingosine-1-phosphate (S1P), a bioactive lipid signaling molecule, is potentially involved in EOC tumorigenesis. We have found that S1P is elevated in human EOC ascites. We show that physiologically relevant concentrations of S1P stimulate migration and invasion of EOC cells but inhibit migration of human ovarian surface epithelial (HOSE) cells. In addition, S1P inhibits lysophosphatidic acid (LPA)-induced cell migration in HOSE but not in EOC cells. We have provided the first line of evidence that the expression levels of S1P receptor subtypes are not the only determinants for how cells respond to S1P. Although S1P(1) is expressed and functional in HOSE cells, the inhibitory effect mediated by S1P(2) is dominant in those cells. The cellular preexisting stress fibers are also important determinants for the migratory response to S1P. Differential S1P-induced morphology changes are noted in EOC and HOSE cells. Preexisting stress fibers in HOSE cells are further enhanced by S1P treatment, resulting in the negative migratory response to S1P. By contrast, EOC cells lost stress fibers and S1P treatment induces filopodium-like structures at cell edges, which correlates with increased cell motility. In addition, inhibition of the protein kinase C pathway is likely to be involved in the inhibitory effect of S1P on LPA-induced cell migration in HOSE cells. These findings are important for the development of new therapeutics targeting S1P and LPA in EOC.
Dongmei Wang; Zhenwen Zhao; Andrea Caperell-Grant; Gong Yang; Samuel C Mok; Jinsong Liu; Robert M Bigsby; Yan Xu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  7     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-22     Completed Date:  2008-09-08     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1993-2002     Citation Subset:  IM    
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MeSH Terms
Ascites / pathology
Cell Line, Tumor
Cell Movement / drug effects*
Cell Shape / drug effects
Enzyme Activation / drug effects
Epithelial Cells / drug effects,  enzymology,  pathology*
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Lysophospholipids / pharmacology*
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
Ovarian Neoplasms / enzymology,  pathology*
Protein Kinase C / metabolism
Receptors, Lysosphingolipid / metabolism
Signal Transduction / drug effects
Sphingosine / analogs & derivatives*,  pharmacology
Stress Fibers / drug effects,  pathology
Grant Support
CA-89228/CA/NCI NIH HHS; R01 CA089228/CA/NCI NIH HHS; R01 CA089228-05/CA/NCI NIH HHS; R01 CA095042/CA/NCI NIH HHS; R01 CA095042/CA/NCI NIH HHS; R01 CA095042-06/CA/NCI NIH HHS
Reg. No./Substance:
0/Lysophospholipids; 0/Receptors, Lysosphingolipid; 22002-87-5/lysophosphatidic acid; 26993-30-6/sphingosine 1-phosphate; EC Kinase C; EC Signal-Regulated MAP Kinases; EC Protein Kinase Kinases; NGZ37HRE42/Sphingosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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