Interestingly, injecting PG1 cells into different microenvironments regarding the RANKL/RANK/OPG system (Figure S5) revealed that only invalidation of Rankl (Rankl-/-) had an impact on the number of lung metastases, independently of RANK expression by the osteosarcoma cells, while either Opg invalidation (Opg-/-) or Rank over-expression in the monocyte/macrophage lineage [RankTg, [33]] had no influence on this number compared to the WT microenvironment. This evidence concerns the gene TNFSF11 and osteosarcoma.