Document Detail


Brain fatty acid-binding protein and omega-3/omega-6 fatty acids: mechanistic insight into malignant glioma cell migration.
MedLine Citation:
PMID:  20834042     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Malignant gliomas (MG) are highly infiltrative tumors that consistently recur despite aggressive treatment. Brain fatty acid-binding protein (FABP7), which binds docosahexaenoic acid (DHA) and arachidonic acid (AA), localizes to sites of tumor infiltration and is associated with a poor prognosis in MG. Manipulation of FABP7 expression in MG cell lines affects cell migration, suggesting a role for FABP7 in tumor infiltration and recurrence. Here, we show that DHA inhibits and AA stimulates migration in an FABP7-dependent manner in U87 MG cells. We demonstrate that DHA binds to and sequesters FABP7 to the nucleus, resulting in decreased cell migration. This anti-migratory effect is partially dependent on peroxisome proliferator-activated receptor γ, a DHA-activated transcription factor. Conversely, AA-bound FABP7 stimulates cell migration by activating cyclooxygenase-2 and reducing peroxisome proliferator-activated receptor γ levels. Our data provide mechanistic insight as to why FABP7 is associated with a poor prognosis in MG and suggest that relative levels of DHA and AA in the tumor environment can make a profound impact on tumor growth properties. We propose that FABP7 and its fatty acid ligands may be key therapeutic targets for controlling the dissemination of MG cells within the brain.
Authors:
Raja Mita; Michael J Beaulieu; Catherine Field; Roseline Godbout
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2011-02-28     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37005-15     Citation Subset:  IM    
Affiliation:
Department of Oncology, School of Cancer, Engineering and Imaging Sciences, Cross Cancer Institute, University of Alberta, Edmonton, Alberta T6G 1Z2.
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acid / metabolism*
Blotting, Western
Carrier Proteins / antagonists & inhibitors,  genetics,  metabolism*
Cell Differentiation
Cell Movement*
Cell Nucleus / metabolism
Cyclooxygenase 2 / chemistry,  metabolism
Docosahexaenoic Acids / metabolism*
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Glioma / metabolism,  pathology*
Humans
Mutagenesis, Site-Directed
Mutation / genetics
PPAR gamma / antagonists & inhibitors,  genetics,  metabolism
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Suppressor Proteins / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/FABP7 protein, human; 0/PPAR gamma; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Tumor Suppressor Proteins; 25167-62-8/Docosahexaenoic Acids; 506-32-1/Arachidonic Acid; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human
Comments/Corrections

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