Bone metastasis: can osteoclasts be excluded?
The RANK/RANKL signalling mechanism is the final common pathway of osteoclast formation and activity. Inhibitors of RANK ligand (RANKL) that bind to RANK (for 'receptor activator of NF-kappaB'), such as osteoprotegerin (OPG), neutralizing antibodies against RANKL and soluble RANK antagonists, are well described inhibitors of bone metastasis in preclinical and clinical models, presumably because of their effects on osteoclasts. Jones et al. show that OPG inhibits bone metastasis after intracardiac injection of B16F10 murine melanoma cells, but claim that bone metastases are entirely independent of osteoclast formation and bone resorption: rather, they are caused by an effect on cell migration through RANK. However, we question whether these surprising conclusions are rigorously supported by their data.
Martin
T John
TJ
St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australiajmartin@svi.edu.au.
Mundy
Gregory R
GR
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D053244:Osteoprotegerin / Q000494:pharmacology / Q000627:therapeutic use; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D015203:Reproducibility of Results
D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B