BoneKEy Reports | BoneKEy Watch

Targeting RANKL may help reduce spread of lung cancer to bone


Bone metastases are common in patients with non-small cell lung cancer (NSCLC). Peng et al. looked at different NSCLC cell lines to measure expression levels of RANK, RANKL and osteoprotegerin (OPG), which are all part of a bone remodeling signaling pathway that regulates osteoclastogenesis and osteoclast activity.

NSCLC cell lines were compared with samples of bone metastases and cells from primary NSCLC tumors. In this latter group of samples, clinicopathological data were available to enable correlation of key parameters with levels of expression of individual proteins.

Higher levels of expression of OPG, RANK and RANKL, and a higher RANKL:OPG ratio detected in NSCLC lines and tumor samples from bone metastases, were associated with a higher risk of metastasis to both lymph nodes and distant sites such as bone. NSCLC cells showed more tendency to migrate and invade tissue, both in vitro and in vivo, when recombinant human RANKL was introduced, or when cells were transfected with RANKL cDNA. Metastatic potential was reduced by adding OPG.

Editor’s comment: These findings suggest that it may be possible to reduce the risk of metastasis in patients with NSCLC by targeting RANKL therapeutically using the monoclonal antibody denosumab.

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