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

被引:73
作者
Petersen, G
Moesgaard, B
Schmid, PC
Schmid, HHO
Broholm, H
Kosteljanetz, M
Hansen, HS
机构
[1] Danish Univ Pharmaceut Sci, Dept Pharmacol, DK-2100 Copenhagen, Denmark
[2] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
[3] Copenhagen Univ Hosp, Rigshosp, Dept Neuropathol, Copenhagen, Denmark
[4] Copenhagen Univ Hosp, Rigshosp, Dept Neurosurg, Copenhagen, Denmark
关键词
anandamide; 2-arachidonoyl glycerol; fatty acid amide hydrolase; N-acylethanolamine; N-acylphosphatidylethanolamine-hydrolysing phospholipase D;
D O I
10.1111/j.1471-4159.2005.03013.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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/mu mol lipid phosphorus) including anandamide (17-fold, 4.6 +/- 3.1pmol/mu mol 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/mu mol lipid phosphorus) including 2-arachidonoyl glycerol (20-fold, 1524 +/- 361 pmol/mu mol 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.
引用
收藏
页码:299 / 309
页数:11
相关论文
共 69 条
[1]  
BARTLETT GR, 1959, J BIOL CHEM, V234, P466
[2]   A new strategy to block tumor growth by inhibiting endocannabinoid inactivation [J].
Bifulco, M ;
Laezza, C ;
Valenti, M ;
Ligresti, A ;
Portella, G ;
Di Marzo, V .
FASEB JOURNAL, 2004, 18 (11) :1606-+
[3]   Targeting the endocannabinoid system in cancer therapy: A call for further research [J].
Bifulco, M ;
Di Marzo, V .
NATURE MEDICINE, 2002, 8 (06) :547-550
[4]   Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth [J].
Bifulco, M ;
Laezza, C ;
Portella, G ;
Vitale, M ;
Orlando, P ;
De Petrocellis, L ;
Di Marzo, V .
FASEB JOURNAL, 2001, 15 (12) :2745-+
[5]   Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas [J].
Blázquez, C ;
González-Feria, L ;
Alvarez, L ;
Haro, A ;
Casanova, ML ;
Guzmán, M .
CANCER RESEARCH, 2004, 64 (16) :5617-5623
[6]   Inhibition of tumor angiogenesis by cannabinoids [J].
Blázquez, C ;
Casanova, ML ;
Planas, A ;
del Pulgar, TG ;
Villanueva, C ;
Fernández-Aceñero, MJ ;
Aragonés, J ;
Huffman, JW ;
Jorcano, JL ;
Guzmán, M .
FASEB JOURNAL, 2003, 17 (01) :529-+
[7]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[8]   Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors [J].
Casanova, ML ;
Blázquez, C ;
Martínez-Palacio, J ;
Villanueva, C ;
Fernández-Aceñero, MJ ;
Huffman, JW ;
Jorcano, JL ;
Guzmán, M .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (01) :43-50
[9]   Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1 [J].
Contassot, E ;
Tenan, M ;
Schnüriger, V ;
Pelte, MF ;
Dietrich, PY .
GYNECOLOGIC ONCOLOGY, 2004, 93 (01) :182-188
[10]   Effect on cancer cell proliferation of palmitoylethanolamide, a fatty acid amide interacting with both the cannabinoid and vanilloid signalling systems [J].
De Petrocellis, L ;
Bisogno, T ;
Ligresti, A ;
Bifulco, M ;
Melck, D ;
Di Marzo, V .
FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2002, 16 (04) :297-302