Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations to clinical and pathological features
Agata M. Wasik1, Lina Nygren1, Stefan Almestrand1, Fang Zong1, Jenny Flygare2, Stefanie Baumgartner Wennerholm3, Leonie Saft4, Patrik Andersson5, Eva Kimby3, Björn E. Wahlin3, Birger Christensson1, and Birgitta Sander1
1 Drug Development Program, Sarah Cannon Research Institute, Denver, CO 80218
2 Department of Investigational Cancer Therapeutics (Phase I Program), U.T. MD Anderson Cancer Center, Houston, TX
3 Department of Biostatistics, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX
4 Department of Symptom Research, U.T. MD Anderson Cancer Center, Houston, TX
5 Moores Cancer Center, University of California San Diego, La Jolla, CA
Correspondence:
Agata M. Wasik, email:
Keywords: mantle cell lymphoma, endocannabinoid system
Received: July 14, 2014 Accepted: August 31, 2014 Published: September 4, 2014
Abstract
The cannabinoid receptors are upregulated in many types of cancers, including mantle cell lymphoma (MCL) and have been suggested to constitute novel therapeutic targets. The expression pattern of the key members of the endocannabinoid system was analyzed in a well-characterized MCL patient cohort and correlated to biological features. 107 tumor tissues were analyzed for the mRNA levels of cannabinoid receptors 1 and 2 (CNR1 and CNR2) and the two main enzymes regulating the endocannabinoid anandamide levels in tissue: NAPEPLD and FAAH (participating in synthesis and degradation, respectively). NAPEPLD, CNR1 and CNR2 were overexpressed while FAAH expression was reduced in MCL compared to non-malignant B-cells. Both low CNR1 and high FAAH levels correlated with lymphocytosis (p=0.016 and p=0.022, respectively) and with leukocytosis (p=0.0018 and p=0.047). Weak to moderate CNR1 levels were a feature of SOX11 negative MCL (p=0.006). Both high CNR2 and high FAAH levels correlated to anemia (p=0.0006 and p=0.038, respectively). In conclusion, the relative expression of the anandamide synthesizing and metabolizing enzymes in MCL is heavily perturbed. This finding, together with high expression of cannabinoid receptors, could favor enhanced anandamide signaling and suggest that targeting the endocannabinoid system might be considered as part of lymphoma therapy.
