| Brain fatty acid-binding protein and omega-3/omega-6 fatty acids: mechanistic insight into malignant glioma cell migration. | |
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MedLine Citation:
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PMID: 20834042 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Raja Mita; Michael J Beaulieu; Catherine Field; Roseline Godbout |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-12 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-15 Completed Date: 2011-02-28 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 37005-15 Citation Subset: IM |
Affiliation:
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Department of Oncology, School of Cancer, Engineering and Imaging Sciences, Cross Cancer Institute, University of Alberta, Edmonton, Alberta T6G 1Z2. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Arachidonic Acid
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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:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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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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