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

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 CB 2 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 CB 2 activation. CB 2 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, CB 2 was expressed with great intensity in tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with CB 2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A direct correlation between CB 2 and SNAIL1 expression was also found in human tumors. CB 2 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 CB 2 should be considered as anti-tumoral therapy. This study was supported by AECC; ISCIIIPI10/00879 (Plan Nacional de I+D+I 2008-2011, FEDER funds co-financed), and ISCIII-RETIC RD12/0036/0041/n(Plan Estatal de I+D+I 2013-2016, FEDER funds cofinanced). JMG and EMM are supported by ISCIII, CP08/00217 and FI11/00696 respectively, (Plan Nacional/nde I+D+I 2008-2011, FEDER funds co-financed).