Alteration of endocannabinoid system in human gliomas

Abstract

J. Neurochem. (2012) 120, 842–849. Abstract Endocannabinoids are neuromodulatory lipids that mediate the central and peripheral neural functions. Endocannabinoids have demonstrated their anti‐proliferative, anti‐angiogenic and pro‐apoptotic properties in a series of studies. In the present study, we investigated the levels of two major endocannabinoids, anandamide and 2‐arachidonylglycerol (2‐AG), and their receptors, CB1 and CB2, in human low grade glioma (WHO grade I‐II) tissues, high grade glioma (WHO grade III‐IV) tissues, and non‐tumor brain tissue controls. We also measured the expressions and activities of the enzymes responsible for anandamide and 2‐AG biosynthesis and degradation, that is, N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D (NAPE‐PLD), fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MGL), and diacylglycerol lipase‐alpha (DGL), in the same samples. Liquid chromatography–mass spectometry analysis showed that the levels of anandamide decreased, whereas the levels of 2‐AG increased in glioma tissues, comparing to the non‐tumor controls. The expression levels and activities of NAPE‐PLD, FAAH and MGL also decreased in glioma tissues. Furthermore, quantitative‐PCR analysis and western‐blot analysis revealed that the expression levels of cananbinoid receptors, CB1 and CB2, were elevated in human glioma tissues. The changes of anandamide and 2‐AG contents in different stages of gliomas may qualify them as the potential endogenous biomarkers for glial tumor malignancy.

The use of cannabinoids as anticancer agents

“…CB1 receptors levels are also increased and correlate with disease severity in human epithelial ovarian tumors (Messalli et al, 2014) and have been proposed to be a factor of bad prognosis following surgery in stage IV colorectal cancer (Jung et al, 2013) Regarding CB2 receptor, a correlation between its expression, histologic grade and prognosis has been demonstrated in breast cancer (Caffarel et al, 2006) and glioma (Sanchez et al, 2001). In this latter tumor type a combined up-regulation of CB1 and CB2 receptors has been proposed to occur together with a decrease on the levels of the enzymes involved in endocannabinoid degradation compared healthy controls (Wu et al, 2012). Similarly expression of CB1 and CB2 is enhanced in mantle cell lymphoma, whilst FAAH expression is reduced compared to non-malignant B-cells (Ek et al, 2002;Islam et al, 2003;Wasik et al, 2014).…”

Comparative Expression Study of the Endo–G Protein Coupled Receptor (GPCR) Repertoire in Human Glioblastoma Cancer Stem-like Cells, U87-MG Cells and Non Malignant Cells of Neural Origin Unveils New Potential Therapeutic Targets

“…In glioma stem like cells, CB1 agonists have been reported to modulate the expression of stem genes [132]. In human glioma tissues, increased expression of cannabinoid receptors (CB1 and CB2) has been reported to correlate with higher tumor grades [133]; but this remains controversial [134], [135], [136]. In other tumors, a role of CNR1 in invasion and metastasis has been reported [137], [138] and the endocanabinoid system has been reported as a promising tool to improve the efficacy of steroids in colon cancer [139].…”

The influence of biomechanical properties and cannabinoids on tumor invasion

“…15 In human glioma reduced anandamide levels, a cannabinoid receptor (CB) 1 and CB2 agonist, were found while the level of the other main CB1 agonist 2-arachidonylglycerol was increased. 16 This indicates that the eCB system is part of the (anti)tumor signaling. Most of the studies analyzing the effects of cannabinoids on tumor cells have focused on apoptosis [17][18][19] or cell cycle arrest.…”