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, 17 (2), 230

Endocannabinoids as Guardians of Metastasis


Endocannabinoids as Guardians of Metastasis

Irmgard Tegeder. Int J Mol Sci.


Endocannabinoids including anandamide and 2-arachidonoylglycerol are involved in cancer pathophysiology in several ways, including tumor growth and progression, peritumoral inflammation, nausea and cancer pain. Recently we showed that the endocannabinoid profiles are deranged during cancer to an extent that this manifests in alterations of plasma endocannabinoids in cancer patients, which was mimicked by similar changes in rodent models of local and metastatic cancer. The present topical review summarizes the complexity of endocannabinoid signaling in the context of tumor growth and metastasis.

Keywords: 2-arachidonoylglycerol; anandamide; angiogenesis; endocannabinoids; immune cells; orphan G-protein coupled receptor.


Figure 1
Figure 1
Tumor growth causes an increase of 2-arachidonoylethanolamide (2-AG) in tumor tissue and plasma and a decrease of ethanolamide endocannabinoids anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA) because the tumor displaces normal tissue and increases fatty acid amide hydrolase (FAAH) expression. It is likely that the tumor itself mainly secretes 2-AG. The endocannabinoids have diverse effects on cannabinoid receptors including the typical cannabinoid receptor 1 and 2 (CB1, CB2), the orphan G-protein coupled receptors (GPRs) 18, 55, 92 and 119 and peroxisome proliferator activated receptor (PPAR) gamma and alpha, and AEA also acts on transient receptor potential family V type 1 (TRPV1), resulting in complex regulation of tumor growth, metastasis, angiogenesis, polarization of tumor-associated macrophages and dendritic cells, T-cell activation and cancer pain. Treatment with exo- and endogenous cannabinoids reduced cancer growth in several rodent models and cell culture experiments [25,26,27,28,29,30,31], but CB2 expression of the tumor itself has been recently associated with poor prognosis in breast cancer [32].

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