| S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells. | |
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MedLine Citation:
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PMID: 18645009 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 7 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-07-22 Completed Date: 2008-09-08 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1993-2002 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, Indiana University, 975 West Walnut Street IB355A, Indianapolis, IN 46202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Ascites
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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 Female Humans 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 | |
ID/Acronym/Agency:
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CA-89228/CA/NCI NIH HHS; R01 CA089228-05/CA/NCI NIH HHS; R01 CA095042/CA/NCI NIH HHS; R01 CA095042-06/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lysophospholipids; 0/Receptors, Lysosphingolipid; 123-78-4/Sphingosine; 22002-87-5/lysophosphatidic acid; 26993-30-6/sphingosine 1-phosphate; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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