Fig. 1.

Some of the systemic factors involved in dissemination and outgrowth of bone metastases. In the pre-metastatic bone, primary tumor-derived circulating factors can affect various tissue microdomains (hematopoietic cells, mesenchymal stromal cells, osteoblasts, osteoclasts, and vascular cells) to make them a hospitable environment for seeding of tumor cells that eventually disseminate from the primary tumor. After tumor cells have disseminated to bone, primary tumor-derived factors and other circulating cytokines of unknown origin can influence colonization of those tumor cells. Likewise, the tumor cells within the bone microenvironment secrete factors that disrupt normal bone homeostasis to fuel metastatic progression. Abbreviations: CAF, cancer-associated fibroblast, see Table 1 for growth factors.