Platelet-derived thromboxane A<sub>2</sub> induces cyclooxygenase-2 and epithelial-mesenchymal transition marker genes in U-87MG human glioblastoma cells

Glioblastoma (GBM) is an aggressive, treatment-resistant brain tumor. Elevated platelet counts are associated with tumor growth, and platelets accumulate in GBM tumors. Our study found that cyclooxygenase (COX)-2 expression and prostaglandin (PG)E₂ biosynthesis increase during the formation of U-87MG GBM cell spheroids. The COX-2 inhibitors celecoxib and rofecoxib inhibited PGE2 biosynthesis and reduced U-87MG spheroid growth. In cocultures of platelets with U-87MG spheroids, enhanced thromboxane (TX)B₂ was reduced by the selective exposure of platelets to aspirin, suggesting a platelet origin. In U-87MG cells, platelets increased the expression of COX-2 and epithelial-mesenchymal transition (EMT) marker genes. We prevented these effects by pretreating platelets with aspirin to inhibit TXA2 biosynthesis or with a TXA2 receptor antagonist. A TXA2 mimetic stimulated the expression of both COX-2 and epithelial-mesenchymal transition (EMT) markers in spheroids. Altogether, these findings indicate that platelet TXA2 induces COX-2 and promotes EMT in U-87MG cells. Aspirin, by inhibiting platelet TXA2, could contribute to reduced tumor growth and invasion in GBM.