SPP1 and neoplasm: In this process, tumour cells initially perform osteoblast mimicry to adjust themselves from a hostile tissue by producing bone matrix proteins (such as OCN, BSP and OPN).74 Simultaneously, tumour cells manipulate direct secretion of cytokines (such as IL-1β, FGF, TGFβ and TNFα) and indirect induction of osteoblast-produced RANKL to orchestrate the formation and activation of osteoclasts.75 Finally, DTC invade the bone site by alteration of bone metabolism.