Figure 1.

Blood vessels guide tumor cells to the bone microenvironment. After they break free from the primary tumor, most cancer cells that enter the circulation are quickly eliminated. A small portion of the circulating tumor cells (CTCs) survives in the blood stream by interacting with platelets, which protects tumor cells from apoptosis caused by local shear stress and immunological reaction. Moreover, clumping of CTCs with platelets reduces blood flow and facilitates adhesion of the tumor cells to the blood vessel wall. CTCs leave the circulation and enter the local bone marrow via transmigration through the endothelial barrier, in part mediated by the secretion of tumor cell-specific factors (for example, microRNA-105). Moreover, local high levels of stromal cell-derived growth factor 1 (SDF-1) derived from endothelial cells and cells from the bone marrow stroma attract C-X-C receptor 4 (CXCR4) expressing CTCs to the local microenvironment.