Moreover, tumor-induced osteolysis and the subsequent release of factors from bone, further enhance tumor growth by creating a vicious cycle that promotes tumor growth in the bone. In this study, we generated bone-tropic and non-bone tropic 786-O RCC cell lines from human 786-O cells via intracardiac injection of SCID mice and identified molecules that may be involved in the metastasis of RCC to bone. Our analyses suggest that Cad11 is an important mediator of 786-O bone metastasis formation. Specifically, we found that Cad11 expression is increased in 786-O cells derived from bone as compared to parental, liver, or lymph node-derived cells. Evidence for the functional impact of this increased expression is also demonstrated. Organ-specific metastasis has been Oligomycin A observed for many cancers; however, the mechanisms that confer organ specificity are only beginning to be understood. Our study provides an approach to address factors critical for bone-specific metastasis. We identified Cad11 as one of the molecules that is upregulated in bone-derived, but not in lymph node or liver-derived 786-O cells. In addition, we showed that knockdown of Cad11 expression in Bo-786-O cells decreased their migration, but not proliferation. Cad11 is a mesenchymal cell adhesion molecule and is the major cadherin family protein expressed in osteoblasts, although lower levels of Cad11 message can be detected also in brain, lung and heart. Thus, Cad11 may contribute to bone metastasis through increasing RCC cell migration or the adhesion of RCC with the osteoblasts present in the bone marrow. As metastasis is a multistep process, it is likely that many other factors contribute to metastatic progression of RCC in bone. Indeed, FACS analysis showed that there were two populations of cells in Bo-786-O cells: one population of cells that was Cad11-positive and another population of cells that was Cad11-negative. These observations suggest that factors other than Cad11 are also involved in the metastasis of 786-O cells to bone. Increases in Cad11 expression in Bo-786-O cells may be due to epithelial-mesenchymal transition. This possibility is supported by recent studies indicating that cadherins play important roles in the process of EMT during both normal embryonic development and cancer progression. During tumor progression in breast, prostate, gastric, and pancreatic cancers, the development of a mesenchymal phenotype and the loss of E-cadherin expression are often associated with the expression of mesenchymal cadherins such as N-cadherin and/or Cad11. EMT is associated with the acquisition of migratory properties that promote metastasis. Interestingly, metastatic 786-O RCC cells in bone express a higher level of Cad11 than those in liver or lymph nodes, suggesting that Cad11 expression in Bo-786-O cells may support other functions uniquely required for bone metastasis in addition to migration.