EBV Conference 2008 Guangzhou - Baylor College of Medicine

218 (RegID: 1225)
Karl Baumforth
Institution: University of Birmingham
e-mail: k.r.baumforth@bham.ac.uk
LMP1 REGULATES THE LIPID PHOSPHATASE, SGGP1 AND THE LEVELS OF
SPHINGOSINE-1-PHOSPHATE, A POTENTIAL THERAPEUTIC TARGET IN HODGKIN’S
LYMPHOMA.
Baumforth KRN, Reynolds GM, Young LS, Rowe M, Woodman CBJ, Murray PG
Posterabstract:
Sphingosine-1-phosphate (S1P) is an extracellular signaling lipid that promotes cellular proliferation and
migration; it can also activate survival and angiogenic pathways. The balance between the levels of
pro-apoptotic lipids, such as ceramide, and S1P provides a rheostat mechanism that determines whether a
cell is sent into the death pathway (via ceramide) or is protected from apoptosis by S1P. Cancer cells
exploit the sphingolipid rheostat by promoting conditions that favor the production of S1P, either through
the upregulation of enzymes that promote S1P generation, or by the downregulation of those that degrade
S1P, such as SGPP1.
In this study, we have shown that when compared to GC B cells, the presumed progenitor of HL, SGGP1
expression is decreased in both HL cell lines and in primary HRS cells. EBV infection down-regulates
SGGP1 in a variety of B cell backgrounds including primary germinal centre B cells, HL cell lines, and
Burkitt’s lymphoma cell lines; this down-regulation can in part be recapitulated by the ectopic expression
of LMP1 in these cells. EBV-induced down-regulation of SGPP1 in HL cells is followed by increased
levels of S1P. Increased levels of S1P in turn increase the proliferation and extend the survival of HL cells.
EBV-induced increases in S1P could contribute to the immortalisation of B cells and to the pathogenesis
of virus-associated cancers, such as HL. We are currently investigating the potential therapeutic targeting
of S1P in these cancers using ASONEPTM, a humanised S1P-specific monoclonal antibody.
EBV Conference 2008 Guangzhou
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