AI Article Synopsis
- RANKL is a cytokine that plays a significant role in the immune and skeletal systems, as well as in cancer development and spread.
- The soluble form of RANKL, though not critical for normal bone function or immune response, has been found to significantly contribute to the formation of bone metastases in cancer.
- Mice lacking soluble RANKL maintained healthy bones and immune systems but showed considerably fewer bone metastases when cancer cells were introduced, indicating that soluble RANKL specifically promotes cancer spread in bones without affecting other tissues.
Article Abstract
Receptor activator of NF-κB ligand (RANKL) is a multifunctional cytokine known to affect immune and skeletal systems, as well as oncogenesis and metastasis. RANKL is synthesized as a membrane-bound molecule, and cleaved into its soluble form by proteases. As the soluble form of RANKL does not contribute greatly to bone remodelling or ovariectomy-induced bone loss, whether soluble RANKL has a role in pathological settings remains unclear. Here we show that soluble RANKL promotes the formation of tumour metastases in bone. Mice that selectively lack soluble RANKL (Tnfsf11) have normal bone homoeostasis and develop a normal immune system but display markedly reduced numbers of bone metastases after intracardiac injection of RANK-expressing melanoma and breast cancer cells. Deletion of soluble RANKL does not affect osteoclast numbers in metastatic lesions or tumour metastasis to non-skeletal tissues. Therefore, soluble RANKL is dispensable for physiological regulation of bone and immune systems, but has a distinct and pivotal role in the promotion of bone metastases.
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| http://dx.doi.org/10.1038/s42255-019-0104-1 | DOI Listing |
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