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Figure 2: Tumour induced bone destruction. In the prostate, an angiogenic switch promotes the secretion of VEGF, leading to various effects on cells, increasing the release of growth factors and activating integrin activity. (1) Proliferation/antiapoptosis: the cells undergo a transformation that increases the proliferation, survival, differentiation, and migration of the tumour cells. (2) Angiogenesis: the actions of VEGF activate angiogenesis—allowing the tumour cells to access nutrients. (3) Intravasation: cells invade into the local stroma and then enter the local vasculature. (4) Dissemination: cancer cells travel to distant target organs. (5) Survival: Cells can undergo apoptosis or stop proliferation after dissemination and need to evade local immune surveillance. (6) Extravasation: invasion of target organ. (7) Colonisation: after surviving dissemination and extravasation of the target site, tumour cells invade the bone and undergo progressive growth. In metastatic bone disease, tumour cells secrete humoral factors that stimulate osteoclastic and osteoblastic recruitment and differentiation. Once these osteoclasts begin to break down bone, growth factors are released, stimulating growth of the tumour cells. This encourages the tumour cells to release factors that further increase bone resorption by osteoclast and stimulate bone formation through the activation of osteoblasts.