CAPER-α alternative splicing regulates the expression of vascular endothelial growth factor ₁₆₅ in Ewing sarcoma cells

Background: TC-71 Ewing sarcoma cells overexpress vascular endothelial growth factor (VEGF) with a shift from the 189 to the 165 isoform. Methods: The effect of CAPER-α on the expression of the VEGF isoforms, tumor growth, and vessel density was analyzed after transfection of TC-71 cells with CAPER-α cDNA or siRNA. Results: CAPER-α correlated inversely with the VEGF ₁₆₅/VEGF ₁₈₉ mRNA ratio. Up-regulation of CAPER-α resulted in decreased tumor growth, tumor vessel density, and chemotactic activity of the cell's supernatant. CAPER-α expression was regulated by EWS/FLI-1 through a protein-protein interaction. Conclusions: Increased VEGF ₁₆₅ expression is secondary to the down-regulation of CAPER-α by EWS/FLI-1. CAPER-α mediates alternative splicing and controls the shift from VEGF ₁₈₉ to VEGF ₁₆₅.