The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly.
This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL.
Previous analysis of tumor-specific constitutional LOH had identified a putative tumor-suppressor gene (LOH18CR) active in osteosarcoma tumorigenesis, which mapped to a subregion of chromosome 18q linked to both familial Paget's disease and FEO.
These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma.