Blockade of LTB4 binding to its receptor, BLT‐2, inhibits Hodgkin and Reed‐Sternberg (HRS) cell growth in‐vitro

Abstract

Classical Hodgkin Lymphoma (cHL) is characterized by the minority presence of HRS cells amongst a heavy infiltrate of inflammatory cells. HRS cells produce a variety of cytokines and chemokines that modulate the inflammatory background.Membrane phospholipids are metabolized to proinflammatory mediators via the cyclooxygenase (COX) or lipoxygenase (LOX) pathways. Many of these eicosanoids act as autocrine and paracrine regulators of physiological cell functions and of tumor cell growth and survival. While COX2 expression has been associated with the pathogenesis of cHL, little is known about the expression of 5‐LOX or its product, LTB4, in HRS cells.This study examines 5‐LOX and LTB4 expression in cHL and their roles in HRS cell survival. Patient samples were stained for LTB4 and its receptors, BLT1 and BLT2; COX2 and 5‐LOX expression. Cultured HRS cell‐lines were serum starved and treated with LTB4 receptor antagonists for 72 hrs and cell viability assessed.Analysis revealed moderate to strong expression of COX2, 5‐LOX, LTB4, BLT1 and BLT2 on HRS cells. HRS cells also upregulated LTB4 receptor expression in response to serum starvation in‐vitro. Treatment of HRS cells with LTB4 receptor antagonists induced significant HRS cell death as compared to vehicle‐treated controls. Our data support the hypothesis that LTB4 may be an important autocrine survival factor for HRS cells.