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Prog Lipid Res. 2013 Oct;52(4):562-70. doi: 10.1016/j.plipres.2013.08.004. Epub 2013 Aug 24.

Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma.

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1
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.

Abstract

Malignant gliomas are the most common adult brain cancers. In spite of aggressive treatment, recurrence occurs in the great majority of patients and is invariably fatal. Polyunsaturated fatty acids are abundant in brain, particularly ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Although the levels of ω-6 and ω-3 polyunsaturated fatty acids are tightly regulated in brain, the ω-6:ω-3 ratio is dramatically increased in malignant glioma, suggesting deregulation of fundamental lipid homeostasis in brain tumor tissue. The migratory properties of malignant glioma cells can be modified by altering the ratio of AA:DHA in growth medium, with increased migration observed in AA-rich medium. This fatty acid-dependent effect on cell migration is dependent on expression of the brain fatty acid binding protein (FABP7) previously shown to bind DHA and AA. Increased levels of enzymes involved in eicosanoid production in FABP7-positive malignant glioma cells suggest that FABP7 is an important modulator of AA metabolism. We provide evidence that increased production of eicosanoids in FABP7-positive malignant glioma growing in an AA-rich environment contributes to tumor infiltration in the brain. We discuss pathways and molecules that may underlie FABP7/AA-mediated promotion of cell migration and FABP7/DHA-mediated inhibition of cell migration in malignant glioma.

KEYWORDS:

AA; ALA; AP; Activator Protein; Arachidonic acid; Astrocytoma; COX; CYP; DGLA; DHA; Docosahexaenoic acid; EPA; Eicosanoids; FABP7 (B-FABP); Fatty acid binding protein; GFAP; GLA; LA; LDL; LOX; Lipid metabolism; MAPK; Malignant glioma; NFI; Nuclear Factor I; PG; PLA(2); PPAR; PPAR response element; PPRE; PUFA; VLDL; arachidonic acid; brain fatty acid binding protein; cis-linoleic acid; cyclooxygenases; cytochrome P450; dihomo-gammalinolenic acid; docosahexaenoic acid; eicosapentaenoic acid; gamma-linolenic acid; glial fibrillary acidic protein; lipoxygenase; low density lipoprotein; mitogen-activated protein kinase; peroxisome proliferator-activated receptor; phospholipase A(2); polyunsaturated fatty acid; prostaglandin; very low density lipoprotein; α-linolenic acid

PMID:
23981365
PMCID:
PMC4461378
DOI:
10.1016/j.plipres.2013.08.004
[Indexed for MEDLINE]
Free PMC Article
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