Figure 2.

PCa cells home to bone by chemo-attractants and colonize through direct association with osteoblasts, where the PCa cells secrete factors that promote osteoblastic responses and the osteoblasts reinforce tumor cell survival and growth. Expression of various chemo-attractants (Osteonectin, TGFβ, CXCL12, VEGF) guide PCa cells to extravasate and home toward the bone. Once in the bone-microenvironment the cancer cells interact with bone-forming osteoblasts via Cadherin-11. Factors like BMP, ET-1, Wnt, or PDGF, secreted from the cancer cells promote the proliferation and differentiation of osteoblasts. In turn the bone-microenvironment secretes soluble factors like FGF, IGF, and TGFβ to promote tumor cell survival and proliferation.