We demonstrate that this neuronal effect on bone metastasis is mediated via the β2AR in bone-forming cells of the host bone marrow environment, and not by a direct effect on metastatic cancer cells, and furthermore that RANKL, whose expression is induced in osteoblasts by sympathetic activation, mediates this effect in vitro and in vivo via its pro-migratory activity. Here, TNFSF11 is linked to cancer.