Bone Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Bone Cancer, including details on symptoms, types, treatment.

Bone metastasis: can osteoclasts be excluded?

Martin TJ, Mundy GR

St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australiajmartin@svi.edu.au.

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.

Published 22 February 2007 in Nature, 445(7130): E19; discussion E19-20.
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