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

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.

Docosahexaenoic acid up‐regulates both PI3K/AKT‐dependent FABP7–PPARγ interaction and MKP3 that enhance GFAP in developing rat brain astrocytes

“…Hence, although there is available evidence suggesting that DHA as a natural ligand of PPAR influences the FABP7 expression (Elsherbiny et al . ), the novelty of our study lies in appraising their link and thoroughly validating the mechanism of FABP7 and PPARγ interactions. We also related these findings to PI3K/AKT that played a pivotal regulatory role in the present investigation.…”

“…; Elsherbiny et al . ). However, impact of DHA on FABP7 together with PPARγ is unexplored in the primary astrocytes.…”

FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling

“…PUFAs are the main component of cell membrane phospholipids bilayer which play pivotal roles in maintaining membrane structure, energy provision, and cell signaling 41,42 . Of note, studies have indicated that PUFAs may be critical for cancer incidence [43][44][45] . PUFAs and its derived metabolites, coordinating signal transduction and microenvironment to accelerate tumor growth and spread.…”

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

“…However, similar to the previously mentioned proteins, caution must be taken, as the studies do not have the temporal resolution to distinguish between transport and uptake secondary to changes in metabolism. Members of the FABP family facilitate the uptake of fatty acid secondary to their metabolism and are important in the trafficking of fatty acids, the regulation of eCB signaling among others, and we refer the reader to several recent reviews (Moulle et al, 2012;Elsherbiny et al, 2013;Schroeder et al, 2016). Of particular interest are recent studies on FAPB-5, which facilitates the uptake of DHA into the brain, and KO reduces brain DHA by approximately 15% and is associated with impaired working and shortterm memory (Pan et al, 2015(Pan et al, , 2016.…”