Document Detail


S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells.
MedLine Citation:
PMID:  18645009     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Dongmei Wang; Zhenwen Zhao; Andrea Caperell-Grant; Gong Yang; Samuel C Mok; Jinsong Liu; Robert M Bigsby; Yan Xu
Related Documents :
6381099 - Biosynthesis of oxytocin in the corpus luteum.
1722869 - Evidence for two antigenically distinct molecular weight variants of prostaglandin h sy...
8860319 - Ontogeny of immunoreactive steroidogenic proteins (adrenodoxin and cytochrome p-450(21)...
3861869 - Do small and large luteal cells of the sheep interact in the production of progesterone?
12566159 - Enucleolation of porcine oocytes.
20149359 - The role of autophagy in follicular development and atresia in rat granulosa cells.
15072839 - Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-he...
11784099 - Cellular dispersion patterns and phenotypes in the developing mouse superior colliculus.
17015179 - Rate of oxidant stress regulates balance between rat gastric mucosa proliferation and a...
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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
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:
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
Chemical
Reg. No./Substance:
0/Lysophospholipids; 0/Receptors, Lysosphingolipid; 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; NGZ37HRE42/Sphingosine
Comments/Corrections

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


Previous Document:  HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excis...
Next Document:  Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase.