1H, 13C and 31P MAS NMR studies of lyophilized brain tumors

Marszałek, Ryszard; Pisklak, Dariusz Maciej; Horsztyński, Dariusz; Wawer, Iwona

doi:10.1016/j.ssnmr.2010.01.001

Cited by 9 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DHA:AA ratio gradually increases upon brain maturation, along with a reduced need for cell migration and down-regulation of FABP7 (54). A number of reports indicate that the DHA:AA ratio is considerably lower in MG compared with adult brain tissue (55,56). Thus, FABP7 may be more likely to be bound to AA than DHA in MG tumors compared with brain tissue.…”

Section: Discussionmentioning

confidence: 99%

Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids

Mita

Beaulieu

Field

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

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 antimigratory effect is partially dependent on peroxisome proliferator-activated receptor ␥, a DHA-activated transcription factor. Conversely, AA-bound FABP7 stimulates cell migration by activating cyclooxygenase-2 and reducing peroxisome proliferatoractivated receptor ␥ 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids

Mita

Beaulieu

Field

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…As mentioned earlier, DHA levels are decreased in malignant glioma tumor samples resulting in a higher AA:DHA in tumor compared to normal brain tissue [12,41]. The upregulation of FABP7 combined with the higher relative availability of AA may thus favor tumor infiltration.…”

Section: Fabp7: Link To Prognosis Migration and Lipid Environmentmentioning

confidence: 81%

“…These findings are in agreement with earlier studies showing that the lipid environment is altered in malignant glioma. Specifically, DHA levels were reduced by ~50% in malignant glioma samples compared to normal brain tissue [12,[40][41]. This reduction was evident whether total lipids or total phospholipids were analyzed.…”

Section: Malignant Glioma: Lipid Metabolism Imbalancementioning

confidence: 95%

“…2) [12,[40][41] suggesting that tumorigenicity is associated with enhanced DHA loss/ metabolism, to the extent that brain DHA loss cannot be compensated for by liver or diet. The mechanisms driving DHA loss while maintaining AA levels and increasing LA content are not clear.…”

Section: Malignant Glioma: Lipid Metabolism Imbalancementioning

confidence: 99%

“…Other reports have shown that cPLA 2 α and its Ser-505-phosphorylated form are rapidly and specifically recruited at sites of actin polymerization such as membrane ruffles and leading edges [92]. A role for cPLA 2 α in actin remodeling may be highly relevant in the context of FABP7/AA inducing malignant glioma cell migration [17][18], especially in light of the fact that: (i) the increase in FABP7-mediated malignant glioma cell migration is accompanied by increased expression of AA-metabolizing enzymes such as COX-2 and its metabolite PGE 2 [18] and (ii) malignant glioma tumor tissues have a readily available supply of AA probably through an increased load of LA [12,41]. However, studies of the detailed mechanisms underlying these observations and potential involvement of cPLA 2 have yet to be carried out.…”

Section: Cytosolic Phospholipase A2mentioning

confidence: 99%

See 2 more Smart Citations

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

Elsherbiny

Emara

Godbout

2013

Progress in Lipid Research

View full text Add to dashboard Cite

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.

show abstract

Metabolomics: Experimental Design, Methodology and Data Analysis

Schripsema

Dagnino

2014

Encyclopedia of Analytical Chemistry

View full text Add to dashboard Cite

Metabolomics can be defined as the area of research that strives to obtain complete metabolic fingerprints, to detect differences between them and to provide hypothesis to explain those differences. This area of research is still rapidly developing into a powerful tool in the study of all types of organisms. This chapter focuses on the practical and efficient application of metabolomics. All different aspects of a metabolomic study are discussed, ranging from the initial questions and experimental design to the instrumental methods and data analysis.

show abstract

1H, 13C and 31P MAS NMR studies of lyophilized brain tumors

Cited by 9 publications

References 23 publications

Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids

Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids

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

Metabolomics: Experimental Design, Methodology and Data Analysis

Contact Info

Product

Resources

About