ALTERED GENE-EXPRESSION IN HUMAN ASTROCYTOMA-CELLS SELECTED FOR MIGRATION - I - THROMBOXANE SYNTHASE

Human glioma cells from a long-term cell line were selected for their ability to migrate on a glioma-derived extracellular matrix. When test ed over 28 serial passages, the migration-selected strain showed a gen etically stable, enhanced migration rate compared with the parental ce lls. Proliferation studies demonstrated that the growth rate of migrat ion-selected cells was slightly arrested. Both the selected strain and the parental culture showed anchorage-independent growth in soft agar ose and were tumorigenic in athymic mice. Using molecular genetic stra tegies' display to isolate genes expressed differentially between the 2 populations, a 300-bp sequence homologous to thromboxane synthase wa s upregulated in the migration-selected cells relative to the parental cells. Expression levels of thromboxane synthase were highly elevated in the migration-selected cells when assessed by RNAse-protection ass ay and by flow cytometry. Two specific thromboxane synthase inhibitors , Dazmegrel and Furegrelate, reduced the migration rate of the migrati on-selected cells to a rate equal to or less than the rate exhibited b y the parental cells, respectively. The inhibitors effect on the paren tal cells was inconsequential. These results suggest that aberrations in the regulation of thromboxane synthase expression or activity may i nfluence the motility of human glioma cells.