Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells.

Abstract

A proportion of patients with Hodgkin lymphoma carry Epstein-Barr virus (EBV), an oncogenic herpesvirus, in their tumor cells. Although it is generally assumed that EBV contributes to the malignant phenotype of Hodgkin lymphoma cells, direct evidence in support of this is lacking. Here we show that EBV infection of Hodgkin lymphoma cells results in the induction of autotaxin, a secreted tumor-associated factor with lysophospholipase-D activity. Up-regulation of autotaxin increased the generation of lysophosphatidic acid (LPA) and led to the enhanced growth and survival of Hodgkin lymphoma cells, whereas specific down-regulation of autotaxin decreased LPA levels and reduced cell growth and viability. In lymphoma tissues, autotaxin expression was mainly restricted to CD30+ anaplastic large-cell lymphomas and Hodgkin lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV positivity (P = .006). Our results identify the induction of autotaxin and the subsequent generation of LPA as key molecular events that mediate the EBV-induced growth and survival of Hodgkin lymphoma cells and suggest that this pathway may provide opportunities for novel therapeutic intervention.

• Authors: Karl R N Baumforth, Joanne R Flavell, Gary M Reynolds, Gillian Davies, Trevor R Pettit, Wenbin Wei, Susan Morgan, Tanya Stankovic, Yasuhiro Kishi, Hiroyuki Arai, Marketa Nowakova, Guy Pratt, Junken Aoki, Michael J O Wakelam, Lawrence S Young, Paul G Murray
• Journal: Blood (Blood) Vol. 106 Issue 6 Pg. 2138-46 (Sep 15 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15933052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Lysophospholipids
• Multienzyme Complexes
• Phosphoric Diester Hydrolases
• Phosphodiesterase I
• alkylglycerophosphoethanolamine phosphodiesterase
• Pyrophosphatases
• Glucose-6-Phosphate Isomerase
• lysophosphatidic acid

Topics

• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Epstein-Barr Virus Infections (metabolism)
• Gene Expression Regulation, Neoplastic
• Glucose-6-Phosphate Isomerase (genetics)
• Glycoproteins (genetics)
• Herpesvirus 4, Human (physiology)
• Hodgkin Disease (etiology, metabolism, pathology, virology)
• Humans
• Lysophospholipids (biosynthesis)
• Multienzyme Complexes (genetics)
• Phosphodiesterase I
• Phosphoric Diester Hydrolases
• Pyrophosphatases
• Up-Regulation