Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival

Abstract

Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer. However, little is known about the role of the ECS in tumor progression. Here we report the correlation between CB2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB2 activation. CB2 mRNA was detected in 28.6% of samples tested. It was more frequent in N+ patients and predicts disease free survival and overall survival in colon cancer. In positive samples, CB2 was expressed with great intensity in tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with CB2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A direct correlation between CB2 and SNAIL1 expression was also found in human tumors. CB2 receptor expression is a poor prognostic marker for colon cancer and the activation of this receptor, with non-apoptotic doses of agonists, could be collaborating with disease progression. These results raise the question whether the activation of CB2 should be considered as anti-tumoral therapy.

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

“…Another recent study also demonstrated that the level of expression of CB 2 receptors correlates with cancer progression and can predict patient survival in colon cancer patients. Such studies showed that high levels of CB 2 receptors correlate with poor prognosis in patients with tumours in advanced stages or with vascular invasion (Martinez-Martinez et al, 2015).…”

Synthesis and biological evaluation of (3′,5′-dichloro-2,6-dihydroxy-biphenyl-4-yl)-aryl/alkyl-methanone selective CB2 inverse agonist

“…[1][2][3] Both receptors, either individually or in combination, have been identified as potential targets for intervention of human diseases including neurodegenerative [4][5][6] and cardiovascular disease, 7-9 diabetes, [10][11][12] and cancer. [13][14][15][16] Within this spectrum of diseases, intervention in neurodegenerative disorders using CB2 agonists and inverse agonists is arguably one of the most exciting developments in the cannabinoid field. Specifically, microglia, the resident immune and inflammatory mediators in the central nervous system (CNS), express CB2 in Alzheimer's 17,18 and Parkinson's disease 19 and amyotrophic lateral sclerosis.…”

Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives

“…Interestingly, cancer patients were found to have a 2.9 times greater probability of nucleotide changes in the CB 1 gene [22], which was found, in a different study, to be hypermethylated in 77% of tumor samples from colon cancer patients [7]. Finally, CB 1 high immunoreactivity was demonstrated to be a significant prognostic factor following surgery in stage IV colorectal cancer [23] and CB 2 receptor mRNA expression significantly correlated with lymph node involvement in cancer patients [24]. Collectively, such results may have theoretical clinical implications in the light of the widespread use of marijuana, potentially able to modify colorectal cancer course.…”