Among them, fibroblasts, endothelial cells, and macrophages targeting GLYhigh malignant cells work together through certain tumor-promoting signaling pathways, including the NAMPT-(ITGA5 + IAGB1), SPP1-(ITGA5 + ITGB1), NAMPT-INSR, and TGFB1 (ACVR1B + TGFBR2) signaling pairs, which interact to mediate uncontrolled tumor proliferation and growth (Figure 6B). This evidence concerns the gene SPP1 and neoplasm.