Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival
Esther Martínez-Martínez1, Irene Gómez1, Paloma Martín2, Antonio Sánchez3, Laura Román3, Eva Tejerina2, Félix Bonilla1, Antonio García Merino3, Antonio García de Herreros4, Mariano Provencio1 and Jose M. García1
1 Department of Medical Oncology, IIS Puerta de Hierro-Majadahonda, Madrid
2 Department of Pathology, IIS Puerta de Hierro-Majadahonda, Madrid
3 Department of Neuroimmunology, IIS Puerta de Hierro-Majadahonda, Madrid
4 Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona
Correspondence:
Jose Miguel García, email:
Keywords: Colorectal cancer, prognosis marker, CB2, Disease free survival, overall survival
Received: November 04, 2014 Accepted: February 06, 2015 Published: February 09, 2015
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.
