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Neuro-Oncology 1999 1(1):3-13; doi:10.1093/neuonc/1.1.3
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© 1999 by the Society forNeuro-Oncology

Thromboxane synthase regulates the migratory phenotype of human gliomacells

Alf Giese2, Christian Hagel, Ella L. Kim, Svenja Zapf, Jasmin Djawaheri, Michael E. Berens and Manfred Westphal

Departments of Neurosurgery [A.G., E.L.K., S.Z., J.D.,M.W.] and Neuropathology [C.H.], University HospitalEppendorf, 20246 Hamburg, Germany; Neuro-OncologyLaboratory [M.E.B.], Barrow Neurological Institute, Phoenix, AZ85013-4496

2 Address correspondence and reprint requests to Alf Giese, MD, Laboratory forBrain Tumor Biology, Department of Neurosurgery, University HospitalEppendorf, 20246 Hamburg, Germany.


  Abstract

The capacity of glial tumor cells to migrate and diffusely infiltratenormal brain compromises surgical eradication of the disease. Identificationof genes associated with invasion may offer novel strategies for anti-invasivetherapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, hasbeen identified by differential mRNA display as being overexpressed in aglioma cell line selected for migration. In this study TXsyn mRNA expressionwas found in a large panel of glioma cell lines but not in a strain of humanastrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glialtumors and in reactive astrocytes, whereas it could not be detected inquiescent astrocytes and oligodendroglia of normal brain. Glioma cell linesshowed a wide range of thromboxane B2 formation, the relativeexpression of which correlated with migration rates of these cells. Migrationwas effectively blocked by specific inhibitors of TXsyn, such as furegrelateand dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were lesseffective. Treatment with specific inhibitors also resulted in a decrease ofintercellular adhesion in glioma cells. These data indicate that TXsyn plays acrucial role in the signal transduction of migration in glial tumors and mayoffer a novel strategy for anti-invasive therapies.

Received August 4, 1998; Accepted October 6, 1998


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