2. Academic Validation
  3. IL20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer

IL20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer

  • J Clin Invest. 2022 Aug 25;e157917. doi: 10.1172/JCI157917.
Yunfei He 1,  Wenqian Luo 1,  Yingjie Liu 1,  Yuan Wang 1,  Chengxin Ma 1,  Qiuyao Wu 1,  Pu Tian 1,  Dasa He 1,  Zhenchang Jia 1,  Xianzhe Lv 1,  Yu-Shui Ma 2,  Haitang Yang 3,  Ke Xu 3,  Xue Zhang 1,  Yansen Xiao 1,  Peiyuan Zhang 1,  Yajun Liang 1,  Da Fu 2,  Feng Yao 3,  Guohong Hu 1
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai, China.
  • 2 Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Shanghai, China.
  • 3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai, China.
PMID: 36006737 DOI: 10.1172/JCI157917
Abstract

Bone is a common site of metastasis in lung Cancer but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL20RB mediated a direct tumoral response to osteoclasts. Tumoral expression of IL20RB was associated with bone metastasis of lung Cancer, and functionally IL20RB promoted metastatic growth of lung Cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete the IL20RB ligand IL19, and IL19 stimulated IL20RB-expressing tumor cells to activate the downstream JAK1-STAT3 signaling and enhanced proliferation of tumor cells in bone. Importantly, blocking IL20RB with a neutralizing antibody significantly suppressed bone metastasis of lung Cancer. Overall, our data revealed a direct pro-tumor role of osteoclastic niche in bone metastasis and supported IL20RB-targeting approaches for metastasis treatment.

Keywords

Cancer; Cell Biology.

Figures
Products