|
|
Blood, 15 September 2005, Vol. 106, No. 6, pp. 2138-2146.
Prepublished online as a Blood First Edition Paper on June 2, 2005; DOI 10.1182/blood-2005-02-0471.
 Previous Article | Next Article 
Submitted February 7, 2005
Accepted May 15, 2005
Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin's lymphoma cells
Karl R Baumforth, Joanne R Flavell, Gary M Reynolds, Gillian Davies, Trevor R Pettitt, Wenbin Wei, Susan Morgan, Tanya Stankovic, Yasuhiro Kishi, Hiroyuki Arai, Marketa Nowakova, Guy Pratt, Junken Aoki, Michael J Wakelam, Lawrence S Young, and Paul G Murray*
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, West Midlands, United Kingdom
Liver Research Laboratories, University of Birmingham, Birmingham, West Midlands, United Kingdom
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
* Corresponding author; email: p.g.murray{at}bham.ac.uk.
A proportion of patients with Hodgkin's lymphoma carry the 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's lymphoma cells, direct evidence in support of this is lacking. Here we show that EBV infection of Hodgkin's lymphoma cells results in the induction of autotaxin, a secreted tumor-associated factor with lysophospholipase-D activity. Upregulation of autotaxin increased the generation of lysophosphatidic acid (LPA) and led to the enhanced growth and survival of Hodgkin's 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-positive anaplastic large cell lymphomas and Hodgkin's lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV-positivity (p=0.006). 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's lymphoma cells and suggest that this pathway may provide opportunities for novel therapeutic intervention.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
LPA signaling stimulates Hodgkin research
- Gerald Niedobitek
Blood 2005 106: 1898-1899.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
S.-C. Liu, Y.-M. Jen, S. S. Jiang, J.-L. Chang, C. A. Hsiung, C.-H. Wang, and J.-L. Juang
G{alpha}12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization
Cancer Res.,
August 1, 2009;
69(15):
6122 - 6130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jansen, M. Andries, R. Derua, E. Waelkens, and M. Bollen
Domain Interplay Mediated by an Essential Disulfide Linkage Is Critical for the Activity and Secretion of the Metastasis-promoting Enzyme Autotaxin
J. Biol. Chem.,
May 22, 2009;
284(21):
14296 - 14302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. P. Saunders, A. Ouellette, R. Bandle, W. C. Chang, H. Zhou, R. N. Misra, E. M. De La Cruz, and D. T. Braddock
Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion
Mol. Cancer Ther.,
October 1, 2008;
7(10):
3352 - 3362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. R.N. Baumforth, A. Birgersdotter, G. M. Reynolds, W. Wei, G. Kapatai, J. R. Flavell, E. Kalk, K. Piper, S. Lee, L. Machado, et al.
Expression of the Epstein-Barr Virus-Encoded Epstein-Barr Virus Nuclear Antigen 1 in Hodgkin's Lymphoma Cells Mediates Up-Regulation of CCL20 and the Migration of Regulatory T Cells
Am. J. Pathol.,
July 1, 2008;
173(1):
195 - 204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Flavell, K. R. N. Baumforth, V. H. J. Wood, G. L. Davies, W. Wei, G. M. Reynolds, S. Morgan, A. Boyce, G. L. Kelly, L. S. Young, et al.
Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells
Blood,
January 1, 2008;
111(1):
292 - 301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G Kapatai and P Murray
Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma
J. Clin. Pathol.,
December 1, 2007;
60(12):
1342 - 1349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-H. Lin, C.-H. Tsai, J.-S. Chu, J.-Y. Chen, K. Takada, and J.-Y. Shew
Dysregulation of HER2/HER3 Signaling Axis in Epstein-Barr Virus-Infected Breast Carcinoma Cells
J. Virol.,
June 1, 2007;
81(11):
5705 - 5713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jansen, N. Callewaert, I. Dewerte, M. Andries, H. Ceulemans, and M. Bollen
An Essential Oligomannosidic Glycan Chain in the Catalytic Domain of Autotaxin, a Secreted Lysophospholipase-D
J. Biol. Chem.,
April 13, 2007;
282(15):
11084 - 11091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tanaka, S. Okudaira, Y. Kishi, R. Ohkawa, S. Iseki, M. Ota, S. Noji, Y. Yatomi, J. Aoki, and H. Arai
Autotaxin Stabilizes Blood Vessels and Is Required for Embryonic Vasculature by Producing Lysophosphatidic Acid
J. Biol. Chem.,
September 1, 2006;
281(35):
25822 - 25830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. van Meeteren, P. Ruurs, C. Stortelers, P. Bouwman, M. A. van Rooijen, J. P. Pradere, T. R. Pettit, M. J. O. Wakelam, J. S. Saulnier-Blache, C. L. Mummery, et al.
Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development.
Mol. Cell. Biol.,
July 1, 2006;
26(13):
5015 - 5022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Pettitt, S. K. Dove, A. Lubben, S. D. J. Calaminus, and M. J. O. Wakelam
Analysis of intact phosphoinositides in biological samples
J. Lipid Res.,
July 1, 2006;
47(7):
1588 - 1596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
