Thromboxane synthase regulates the migratory phenotype of human glioma cells
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Thromboxane synthase regulates the migratory phenotype of human glioma cells. / Giese, A; Hagel, C; Kim, E L; Zapf, S; Djawaheri, J; Berens, M E; Westphal, M.
in: NEURO-ONCOLOGY, Jahrgang 1, Nr. 1, 01.01.1999, S. 3-13.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Thromboxane synthase regulates the migratory phenotype of human glioma cells
AU - Giese, A
AU - Hagel, C
AU - Kim, E L
AU - Zapf, S
AU - Djawaheri, J
AU - Berens, M E
AU - Westphal, M
PY - 1999/1/1
Y1 - 1999/1/1
N2 - The capacity of glial tumor cells to migrate and diffusely infiltrate normal brain compromises surgical eradication of the disease. Identification of genes associated with invasion may offer novel strategies for anti-invasive therapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, has been identified by differential mRNA display as being overexpressed in a glioma cell line selected for migration. In this study TXsyn mRNA expression was found in a large panel of glioma cell lines but not in a strain of human astrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glial tumors and in reactive astrocytes, whereas it could not be detected in quiescent astrocytes and oligodendroglia of normal brain. Glioma cell lines showed a wide range of thromboxane B2 formation, the relative expression of which correlated with migration rates of these cells. Migration was effectively blocked by specific inhibitors of TXsyn, such as furegrelate and dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were less effective. Treatment with specific inhibitors also resulted in a decrease of intercellular adhesion in glioma cells. These data indicate that TXsyn plays a crucial role in the signal transduction of migration in glial tumors and may offer a novel strategy for anti-invasive therapies.
AB - The capacity of glial tumor cells to migrate and diffusely infiltrate normal brain compromises surgical eradication of the disease. Identification of genes associated with invasion may offer novel strategies for anti-invasive therapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, has been identified by differential mRNA display as being overexpressed in a glioma cell line selected for migration. In this study TXsyn mRNA expression was found in a large panel of glioma cell lines but not in a strain of human astrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glial tumors and in reactive astrocytes, whereas it could not be detected in quiescent astrocytes and oligodendroglia of normal brain. Glioma cell lines showed a wide range of thromboxane B2 formation, the relative expression of which correlated with migration rates of these cells. Migration was effectively blocked by specific inhibitors of TXsyn, such as furegrelate and dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were less effective. Treatment with specific inhibitors also resulted in a decrease of intercellular adhesion in glioma cells. These data indicate that TXsyn plays a crucial role in the signal transduction of migration in glial tumors and may offer a novel strategy for anti-invasive therapies.
KW - Arachidonic Acids
KW - Aspirin
KW - Astrocytes
KW - Benzofurans
KW - Brain Neoplasms
KW - Cell Adhesion
KW - Cell Movement
KW - Enzyme Induction
KW - Enzyme Inhibitors
KW - GTP-Binding Proteins
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic
KW - Glioma
KW - Humans
KW - Imidazoles
KW - Indomethacin
KW - Lysine
KW - Models, Biological
KW - Neoplasm Proteins
KW - Neoplastic Stem Cells
KW - Oligodendroglia
KW - Pentanoic Acids
KW - Phenotype
KW - Pyridines
KW - RNA, Messenger
KW - RNA, Neoplasm
KW - Signal Transduction
KW - Thromboxane B2
KW - Thromboxane-A Synthase
KW - Tumor Cells, Cultured
M3 - SCORING: Journal article
C2 - 11550298
VL - 1
SP - 3
EP - 13
JO - NEURO-ONCOLOGY
JF - NEURO-ONCOLOGY
SN - 1522-8517
IS - 1
ER -