Table 1.Mobilization of disseminated tumor cells

Blocking Chemotaxis to Inhibit Metastatic Homing
Hematopoietic growth factors such as granulocyte stimulating factor (G.CSF) have widely been used to mobilize HSC into the blood stream by promoting the degradation of CXCL12 via two osteoclast proteases, MMP9 and cathepsin K. 8,9 The CXCR4 receptor can be targeted by an antagonist (e.g.AMD3100), inducing HSC mobilization.10 Due to the shared homing cytokines of HSC and metastatic tumor cells, in vivo metastasis of PCa in a mouse model was successfully prevented by inhibiting the CXCL12 pathway and may be prevented in the metastasis of other solid tumors as well.8 Recall that HSC and PCa share a common adhesion molecule receptor for annexin II, which is produced on the surface of osteoblasts, and used in the bone marrow homing process. Blocking annexin II or its receptor prevents both PCa and HSC from localizing to the marrow.15,62.
An In Vivo Experimental Model
If PCa target the HSC niche, then it should also be possible to induce PCa cells to reenter the peripheral circulation by interfering with CXCR4/CXCL12 signaling as have been shown for HSC. To explore this possibility, disseminated PCa cells were first established in bone following tumor implantation. Following removal of the primary tumors, the animals were rested and then treated with AMD3100 or vehicle. Blood was collected 24 hours following the last AMD3100 injection and the number of circulating PCa determined. More circulating PCa cells were found in blood following AMD3100 treatments vs. vehicle treatments. As expected, AMD310 mobilized the HSCs from the marrow. These data suggest that disseminated PCa target HSC niche through the CXCR4/CXCL12 pathway.19

From: The Hematopoietic Stem Cell Niche and Bone Metastasis

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