Figure 5.

Prostate cancer engages bone cells to promote metastatic growth. Prostate cancer (PCa) recruitment to bone involves myriad pathways including the CXCL12/CXCR4 axis. Osteocytes may also recruit PCa to bone via production of CCL5. Once in bone, PCa binds to the endosteal surface via annexin A2 binding. Growth factors released from the bone matrix by osteoclasts such as TGF-β₁ promote PCa growth. Further breakdown of the bone matrix is accomplished by osteocyte production of matrix metalloproteinases (MMPs). Calcium donation through gap junctions between PCa and osteoblasts may also promote PCa growth and metastasis. However, osteoblast production of Wnt5a has been shown to induce dormancy in PCa. Further, the production of GDF10 and TGF-β₂ by osteoblasts induces quiescence in PCa cells. Thus, bone cells may also act as sentries against PCa growth.