Dataset Information

Immunohistochemical assessment of cannabinoid type-1 receptor (CB1R) and its correlation with clinicopathological parameters in glioma.

ABSTRACT:

Background

Glioma is the most frequent primary brain tumor and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors. This study aimed to investigate the immunohistochemical expression level of cannabinoid type-1 receptors (CB1R) in human glioma samples and evaluate its clinicopathologic significance.

Materials and methods

We analyzed the expression of CB1R in 61 paraffin-embedded glioma and 4 normal brain tissues using automated immunohistochemical assay. CB1R expression was categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and phosphorylated extracellular signal-related kinase (p-ERK) expression levels and the clinicopathologic features of glioma.

Results

Our results showed that CB1R immunopositivity was seen in 59 of 61 cases (96.7%). CB1R was down-expressed in glioma compared to normal brain tissues. However, CB1R expression was not correlated with clinicopathological parameters except for p-ERK.

Conclusion

Our findings indicate the down-expression of CB1R in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas should be further tested regardless of the clinicopathological findings to provide a therapeutic advantage in glioma patients.

SUBMITTER: Choucair N

PROVIDER: S-EPMC9248256 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:CB1 cannabinoid receptors (CB1R) are one of the most abundantly expressed G protein coupled receptors (GPCR) in the CNS and regulate diverse neuronal functions. The identification of GPCR interacting proteins has provided additional insight into the fine-tuning and regulation of numerous GPCRs. The cannabinoid receptor interacting protein 1a (CRIP1a) binds to the distal carboxy terminus of CB1R, and has been shown to alter CB1R-mediated neuronal function [1]. The mechanisms by which CRIP1a regulates CB1R activity have not yet been identified; therefore the focus of this investigation is to examine the cellular effects of CRIP1a on CB1R signaling using neuronal N18TG2 cells stably transfected with CRIP1a over-expressing and CRIP1a knockdown constructs. Modulation of endogenous CRIP1a expression did not alter total levels of CB1R, ERK, or forskolin-activated adenylyl cyclase activity. When compared to WT cells, CRIP1a over-expression reduced basal phosphoERK levels, whereas depletion of CRIP1a augmented basal phosphoERK levels. Stimulation of phosphoERK by the CB1R agonists WIN55212-2, CP55940 or methanandamide was unaltered in CRIP1a over-expressing clones compared with WT. However, CRIP1a knockdown clones exhibited enhanced ERK phosphorylation efficacy in response to CP55940. In addition, CRIP1a knockdown clones displayed a leftward shift in CP55940-mediated inhibition of forskolin-stimulated cAMP accumulation. CB1R-mediated Gi3 and Go activation by CP99540 was attenuated by CRIP1a over-expression, but robustly enhanced in cells depleted of CRIP1a. Conversely, CP55940-mediated Gi1 and Gi2 activation was significant enhanced in cells over-expressing CRIP1a, but not in cells deficient of CRIP1a. These studies suggest a mechanism by which endogenous levels of CRIP1a modulate CB1R-mediated signal transduction by facilitating a Gi/o protein subtype preference for Gi1 and Gi2, accompanied by an overall suppression of G-protein-mediated signaling in neuronal cells.