Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue

G. Petersen, B. Moesgaard, Harald S. Hansen, P.C. Schmid, H.H.O. Schmid, H. Broholm, M. Kosteljanetz

    68 Citationer (Scopus)

    Abstract

    The endogenous levels of the two cannabinoid receptor ligands 2-arachidonoyl glycerol and anandamide, and their respective congeners, monoacyl glycerols and N-acylethanolamines, as well as the phospholipid precursors of N-acylethanolamines, were measured by gas chromatography-mass spectrometry in glioblastoma (WHO grade IV) tissue and meningioma (WHO grade I) tissue and compared with human non-tumour brain tissue. Furthermore, the metabolic turnover of N-acylethanolamines was compared by measurements of the enzymatic activity of N-acyltransferase, N-acylphosphatidylethanolamine-hydrolysing phospholipase D and fatty acid amide hydrolase in the same three types of tissue. Glioblastomas were characterized by enhanced levels of N-acylethanolamines (eightfold, 128 ± 59 pmol/µmol lipid phosphorus) including anandamide (17-fold, 4.6 ± 3.1 pmol/µmol lipid phosphorus) and several species of N-acylphosphatidylethanolamines (three to eightfold). This was accompanied by a more than 60% reduction in the enzyme activities of N- acylphosphatidylethanolamine-hydrolysing phospholipase D and fatty acid amide hydrolase. By contrast, meningiomas were characterized by a massively enhanced level of 2-monoacyl glycerols (20-fold, 2293 ± 361 pmol/µmol lipid phosphorus) including 2-arachidonoyl glycerol (20-fold, 1524 ± 361 pmol/µmol lipid phosphorus). This was accompanied by an enhanced in vitro conversion of phosphatidylcholine to monoacyl glycerol (fivefold). The enhanced level of the 2-arachidonoyl glycerol, anandamide and other N-acylethanolamines detected in the two types of tumour tissue may possibly act as endogenous anti-tumour mediators by stimulation of both cannabinoid and non-cannabinoid receptor-mediated mechanisms.
    OriginalsprogEngelsk
    TidsskriftJournal of Neurochemistry
    Vol/bind93
    Udgave nummer2
    Sider (fra-til)299-309
    Antal sider11
    ISSN0022-3042
    DOI
    StatusUdgivet - 1 apr. 2005

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