Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system

Sredni, Simone Treiger; Huang, Chiang Ching; Suzuki, Mario; Pundy, Tatiana; Chou, Pauline M.; Tomita, Tadanori

doi:10.1007/s00381-016-3243-7

Cited by 28 publications

(18 citation statements)

References 21 publications

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“…However, recent studies have demonstrated opposite results, showing CB 1 receptors to be highly expressed in high‐grade gliomas compared to low‐grade tumours and healthy brain samples (Wu et al, ). Interestingly, these results have also been found in samples of low‐grade paediatric glioma, where overexpression has been associated with tumour regression, due to the apoptosis and cell cycle arrest induced by activation of CB 1 receptors by endocannabinoids (Sredni et al, ). Concerning CB 2 receptors, Schley et al .…”

Section: Endocannabinoid System Expression In Cancermentioning

confidence: 74%

Insights into the effects of the endocannabinoid system in cancer: a review

Fraguas-Sánchez

Martín-Sabroso

Torres-Suárez

2018

British J Pharmacology

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In the last few decades, the endocannabinoid system has attracted a great deal of interest in terms of its applications to clinical medicine. In particular, its applications in cancer probably represent one of the therapeutic areas with most promise. On the one hand, expression of the endocannabinoid system is altered in numerous types of tumours, compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type. On the other hand, cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells and also tumour angiogenesis. However, some cannabinoids, at lower concentrations, may increase tumour proliferation, inducing cancer growth. Enough data has been provided to consider the endocannabinoid system as a new therapeutic target in cancer, although further studies to fully establish the effect of cannabinoids on tumour progression are still needed.

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Section: Endocannabinoid System Expression In Cancermentioning

confidence: 74%

Insights into the effects of the endocannabinoid system in cancer: a review

Fraguas-Sánchez

Martín-Sabroso

Torres-Suárez

2018

British J Pharmacology

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“…Previous studies have reported that synapse loss in noise and age-induced hearing loss ( Sergeyenko et al, 2013 ; Espejo-Porras et al, 2015 ; Liberman and Kujawa, 2017 ) which was not associated with loss of OHCs or ABR threshold shifts. This type of cochlea synaptopathy is known as “hidden hearing loss” ( Liberman and Kujawa, 2017 ) and is detected by a reduction in wave I supra-threshold amplitude ( Sredni et al, 2016 ; Liberman and Kujawa, 2017 ). The present study revealed an important “tonic” role of the endocannabinoid/CB2R system to preserve synaptic integrity under normal condition which was unmasked by the application of CB2R antagonist.…”

Section: Discussionmentioning

confidence: 99%

The Endocannabinoid/Cannabinoid Receptor 2 System Protects Against Cisplatin-Induced Hearing Loss

Ghosh

Sheth

Sheehan

et al. 2018

Front. Cell. Neurosci.

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Previous studies have demonstrated the presence of cannabinoid 2 receptor (CB2R) in the rat cochlea which was induced by cisplatin. In an organ of Corti-derived cell culture model, it was also shown that an agonist of the CB2R protected these cells against cisplatin-induced apoptosis. In the current study, we determined the distribution of CB2R in the mouse and rat cochleae and examined whether these receptors provide protection against cisplatin-induced hearing loss. In a knock-in mouse model expressing the CB2R tagged with green fluorescent protein, we show distribution of CB2R in the organ of Corti, stria vascularis, spiral ligament and spiral ganglion cells. A similar distribution of CB2R was observed in the rat cochlea using a polyclonal antibody against CB2R. Trans-tympanic administration of (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), a selective agonist of the CB2R, protected against cisplatin-induced hearing loss which was reversed by blockade of this receptor with 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630), an antagonist of CB2R. JWH015 also reduced the loss of outer hair cells (OHCs) in the organ of Corti, loss of inner hair cell (IHC) ribbon synapses and loss of Na+/K+-ATPase immunoreactivity in the stria vascularis. Administration of AM630 alone produced significant hearing loss (measured by auditory brainstem responses) which was not associated with loss of OHCs, but led to reductions in the levels of IHC ribbon synapses and strial Na+/K+-ATPase immunoreactivity. Furthermore, knock-down of CB2R by trans-tympanic administration of siRNA sensitized the cochlea to cisplatin-induced hearing loss at the low and middle frequencies. Hearing loss induced by cisplatin and AM630 in the rat was associated with increased expression of genes for oxidative stress and inflammatory proteins in the rat cochlea. In vitro studies indicate that JWH015 did not alter cisplatin-induced killing of cancer cells suggesting this agent could be safely used during cisplatin chemotherapy. These data unmask a protective role of the cochlear endocannabinoid/CB2R system which appears tonically active under normal conditions to preserve normal hearing. However, an exogenous agonist is needed to boost the activity of endocannabinoid/CB2R system for protection against a more traumatic cochlear insult, as observed with cisplatin administration.

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“…Initial studies showed that cannabinoids can induce apoptosis of glioma cells via CB1R and CB2R dependent de novo synthesis of the sphingolipid ceramide showing pro-apoptotic properties [47,94,[134][135][136][137]. CB1R is over-expressed in glioblastomas [138] and paediatric low-grade gliomas, and is implicated in tumour involution induced by apoptosis and cell-cycle arrest upon activation [139]. CB 2 R is also highly expressed in glioblastomas and astrocytomas and related to tumour grade [94,137,138,140,141].…”

Section: Central Nervous System Malignanciesmentioning

confidence: 99%

The Interplay between Cancer Biology and the Endocannabinoid System—Significance for Cancer Risk, Prognosis and Response to Treatment

Moreno

Čavić

Krivokuća

et al. 2020

Cancers

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The various components of the endocannabinoid system (ECS), such as the cannabinoid receptors (CBRs), cannabinoid ligands, and the signalling network behind it, are implicated in several tumour-related states, both as favourable and unfavourable factors. This review analyses the ECS’s complex involvement in the susceptibility to cancer, prognosis, and response to treatment, focusing on its relationship with cancer biology in selected solid cancers (breast, gastrointestinal, gynaecological, prostate cancer, thoracic, thyroid, CNS tumours, and melanoma). Changes in the expression and activation of CBRs, as well as their ability to form distinct functional heteromers affect the cell’s tumourigenic potential and their signalling properties, leading to pharmacologically different outcomes. Thus, the same ECS component can exert both protective and pathogenic effects in different tumour subtypes, which are often pathologically driven by different biological factors. The use of endogenous and exogenous cannabinoids as anti-cancer agents, and the range of effects they might induce (cell death, regulation of angiogenesis, and invasion or anticancer immunity), depend in great deal on the tumour type and the specific ECS component that they target. Although an attractive target, the use of ECS components in anti-cancer treatment is still interlinked with many legal and ethical issues that need to be considered.

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Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system

Cited by 28 publications

References 21 publications

Insights into the effects of the endocannabinoid system in cancer: a review

Insights into the effects of the endocannabinoid system in cancer: a review

The Endocannabinoid/Cannabinoid Receptor 2 System Protects Against Cisplatin-Induced Hearing Loss

The Interplay between Cancer Biology and the Endocannabinoid System—Significance for Cancer Risk, Prognosis and Response to Treatment

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