論文

査読有り 国際誌
2019年9月

Soluble RANKL is physiologically dispensable but accelerates tumour metastasis to bone.

Nature metabolism
  • Tatsuo Asano
  • ,
  • Kazuo Okamoto
  • ,
  • Yuta Nakai
  • ,
  • Masanori Tsutsumi
  • ,
  • Ryunosuke Muro
  • ,
  • Ayako Suematsu
  • ,
  • Kyoko Hashimoto
  • ,
  • Tadashi Okamura
  • ,
  • Shogo Ehata
  • ,
  • Takeshi Nitta
  • ,
  • Hiroshi Takayanagi

1
9
開始ページ
868
終了ページ
875
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s42255-019-0104-1

Receptor activator of NF-κB ligand (RANKL) is a multifunctional cytokine known to affect immune and skeletal systems, as well as oncogenesis and metastasis1-4. RANKL is synthesized as a membrane-bound molecule, and cleaved into its soluble form by proteases5-7. As the soluble form of RANKL does not contribute greatly to bone remodelling or ovariectomy-induced bone loss8, 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 (Tnfsf11ΔS/ΔS)5-7,9 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.

リンク情報
DOI
https://doi.org/10.1038/s42255-019-0104-1
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32694743

エクスポート
BibTeX RIS