S100A4 expression has been reported to induce the expression and secretion of OPN in osteosarcoma cells through the NF-κB-dependent signaling, while extracellular S100A4 mediates OPN-dependent induction of proteolytic activity, which further increases osteosarcoma cell invasion and metastasis as well as angiogenesis [151]. This evidence concerns the gene SPP1 and osteosarcoma.