It is of interest to examine whether silencing Cad11 in Bo-786-O cells can decrease RCC bone metastasis. Our attempts to address this question were inconclusive as a majority of animals injected with Bo-786-O cells with or without knockdown of Cad11 did not survive long enough for further analysis of tumors in bone. We have performed x-ray, microCT, and histology on mice injected with 786-O cells in order to determine whether an osteolytic or osteoblastic reaction occurs, and did not detect obvious osteolytic lesions due to insufficient tumor growth in bone. This problem may be unique to 786-O cells, as we did not encounter such a problem when injecting mice with PC3-mm2 prostate cancer cells. Thus, whether an increase in Cad11 expression alone is sufficient to increase RCC bone RG7204 Raf inhibitor metastasis requires further study. CXCR4 is another adhesion molecule that has been implicated in the acquisition of invasive and metastatic phenotypes in several cancer types, such as breast cancer, melanoma, prostate cancer and renal cancer. Studies have shown that higher CXCR4 expression is strongly associated with advanced RCC and in RCC metastasis. Our observations that CXCR4 expression was elevated in metastatic cell lines from bone and other organs, suggesting that CXCR4 may play a role in 786-O cells metastasis, but not specifically to the bone. The hypervascularity of RCC is attributed to the mutation of the VHL tumor suppressor gene. Indeed, 786-O harbors an inactivating mutation in one VHL allele, while the second allele is deleted. Our study revealed that the gene expression levels of angiogenic molecules such as HIF-1a and VEGF in 786-O cell lines were relatively high. However, we did not detect significant differences in the gene expression among metastatic cell lines derived from organs. These results indicate that although angiogenesis plays an important role in the development and metastasis of RCC due to the loss of VHL function, it is not specific to bone metastasis. The angiopoietinTie-2 signaling axis is an alternative pathway to promote angiogenesis. However, the role of Ang-1 in tumor angiogenesis remains controversial. Some studies suggested that Ang-1 is angiogenic, whereas, others indicated that it inhibits angiogenesis, tumor growth and vascular permeability. We found that Ang1 message is decreased in organ-derived 786-O RCC cells. However, whether this leads to a decrease in protein expression was not examined. The significance of Ang1 in 786-O bone metastasis is not clear and therefore requires further study. Bone lesions in patients with RCC are exclusively osteolytic. In many cancers, like breast and prostate cancers, tumorproduced growth factors or cytokines like PTHrP, RANKL, and IL-6 play important roles in bone osteolysis. Contrasting evidence has been found.