Moreover, analysis of mouse GBM tumors showed that Spp1 is robustly up-regulated in the cell cluster of ECs-2 (Fig. 6E), which was characterized as a mesenchymal-like population of ECs with up-regulated Twist1 expression and potential ability to induce Mφ immunosuppression (Fig. 1), suggesting ECs as another major source of OPN production, in addition to macrophages and glioma cells (24, 25). Here, TWIST1 is linked to central nervous system cancer.