Chemokines and their receptors might be involved in the selection of specific organs by metastatic cancer cells. For instance, the CXCR4-SDF-1␣ pair regulates adhesion and migration of breast as well as prostate cancer cells to metastatic sites. In this study, we present the first evidence for the expression of CX3CR1-the specific receptor for the chemokine fractalkine-by human prostate cancer cells, whereas human bone marrow endothelial cells and differentiated osteoblasts express fractalkine. The adhesion of prostate cancer cells to human bone marrow endothelial cells in flow conditions is significantly reduced by a neutralizing antibody against fractalkine, and they migrate toward a medium conditioned by osteoblasts, which secrete the soluble form of the chemokine. Finally, fractalkine activates the PI3K/Akt survival pathway in human prostate cancer cells.