TY - JOUR
T1 - Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells
AU - Baumforth, Karl
AU - Gough, Joanne
AU - Reynolds, Gary
AU - Davies, G
AU - Pettitt, Trevor
AU - Wei, Wenbin
AU - Morgan, Susan
AU - Stankovic, Tatjana
AU - Kishi, Y
AU - Arai, H
AU - Nowakova, M
AU - Pratt, Guy
AU - Aoki, J
AU - Wakelam, Michael
AU - Young, Lawrence
AU - Murray, Paul
PY - 2005/9/15
Y1 - 2005/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=24744462717&partnerID=8YFLogxK
U2 - 10.1182/blood-2005-02-0471
DO - 10.1182/blood-2005-02-0471
M3 - Article
C2 - 15933052
SN - 1528-0020
VL - 106
SP - 2138
EP - 2146
JO - Blood
JF - Blood
ER -