Dysregulation of developmental pathways in bone metastasis.

It is well-known that pathways normally functioning during embryonic development are dysregulated in cancer. Experimental and clinical studies have established strong connections between aberrant developmental pathways and transformation, as well as other early stage events of cancer progression. There is now emerging evidence that also indicates the contribution of developmental pathways to the pathogenesis of distant metastasis, including bone metastasis. In particular, the Wnt, BMP, and Hedgehog signaling pathways have all been implicated in the development of bone metastasis. These developmental pathways participate in the regulation of cell-autonomous functions in tumor cells as well as tumor-stromal interactions in the bone microenvironment, eventually promoting the formation of osteolytic or osteoblastic bone metastasis.