Fig. 3.

Tumor cells are recruited by the bone marrow where they alter the osteoblasts and osteoclast balance. SDF-1, which is abundantly present in the bone marrow, attracts CXCR-4 expressing tumor cells. When in the bone marrow tumor cells interact with osteoblasts and osteoclast precursor cells through the production of PTHrP, RANKL and other osteoclast activating factors. Alternatively, tumor cells stimulate MSC to make IL-6. As a result, osteoclasts are activated. Tumor cells also inhibit osteoblast activity and new bone formation by blocking the Wnt pathway via the production of Dkk1. This leads to an increase in bone degradation and release of growth factors