The advantage of this strategy, compared to using a RANKL blocker like OPG, was that it allowed us to assess whether sympathetic activation promotes breast cancer bone colonization via the pro-migratory effect of RANKL on metastatic cancer cells or via an indirect stimulatory effect on bone turnover, since sympathetic activation increases bone remodeling, potentially increasing the expression, activity, and/or availability of other cell- or ECM-derived cytokines promoting cancer cell bone colonization, establishment, and growth. The gene discussed is TNFSF11; the disease is breast carcinoma.