Expression and Functional Relevance of Cannabinoid Receptor 1 in Hodgkin Lymphoma

Alexander H Benz,Urszula Grabiec,Marco Koch,Erik Maronde,Martin-Leo Hansmann,Faramarz Dehghani,Sylvia Hartmann,Christoph Renné,Sebastian Newrzela,Benjamin Rengstl,Sonja Kallendrusch

doi:10.1371/journal.pone.0081675

Abstract

BackgroundCannabinoid receptor 1 (CB1) is expressed in certain types of malignancies. An analysis of CB1 expression and function in Hodgkin lymphoma (HL), one of the most frequent lymphomas, was not performed to date.Design and MethodsWe examined the distribution of CB1 protein in primary cases of HL. Using lymphoma derived cell lines, the role of CB1 signaling on cell survival was investigated.ResultsA predominant expression of CB1 was found in Hodgkin-Reed-Sternberg cells in a vast majority of classical HL cases. The HL cell lines L428, L540 and KM-H2 showed strong CB1-abundance and displayed a dose-dependent decline of viability under CB1 inhibition with AM251. Further, application of AM251 led to decrease of constitutively active NFκB/p65, a crucial survival factor of HRS-cells, and was followed by elevation of apoptotic markers in HL cells.ConclusionsThe present study identifies CB1 as a feature of HL, which might serve as a potential selective target in the treatment of Hodgkin lymphoma.

Highlights

The Endocannabinoid system consists of cannabinoid receptors, their endogenous, exogenous or synthetic ligands and the enzymes responsible for synthesis and degradation of endogenous ligands
A predominant expression of Cannabinoid receptor 1 (CB1) was found in Hodgkin-Reed-Sternberg cells in a vast majority of classical Hodgkin lymphoma (HL) cases
Application of AM251 led to decrease of constitutively active NFkB/p65, a crucial survival factor of Hodgkin and multinucleated Reed-Sternberg (HRS-)cells, and was followed by elevation of apoptotic markers in HL cells

Summary

Results

A predominant expression of CB1 was found in Hodgkin-Reed-Sternberg cells in a vast majority of classical HL cases. Application of AM251 led to decrease of constitutively active NFkB/p65, a crucial survival factor of HRS-cells, and was followed by elevation of apoptotic markers in HL cells

Introduction

Materials and Methods

Discussion