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IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer
Yunfei He, … , Feng Yao, Guohong Hu
Yunfei He, … , Feng Yao, Guohong Hu
Published August 25, 2022
Citation Information: J Clin Invest. 2022;132(20):e157917. https://doi.org/10.1172/JCI157917.
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Research Article Cell biology Article has an altmetric score of 17

IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer

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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 IL receptor 20 subunit β (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL-20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete the IL-20RB ligand IL-19, and IL-19 stimulated IL-20RB–expressing tumor cells to activate downstream JAK1/STAT3 signaling, leading to enhanced proliferation of tumor cells in bone. Importantly, blocking IL-20RB with a neutralizing antibody significantly suppressed bone metastasis of lung cancer. Overall, our data revealed a direct protumor role of osteoclastic niche in bone metastasis and supported IL-20RB–targeting approaches for metastasis treatment.

Authors

Yunfei He, Wenqian Luo, Yingjie Liu, Yuan Wang, Chengxin Ma, Qiuyao Wu, Pu Tian, Dasa He, Zhenchang Jia, Xianzhe Lv, Yu-Shui Ma, Haitang Yang, Ke Xu, Xue Zhang, Yansen Xiao, Peiyuan Zhang, Yajun Liang, Da Fu, Feng Yao, Guohong Hu

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Figure 1

IL20RB expression is associated with lung cancer bone metastasis.

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IL20RB expression is associated with lung cancer bone metastasis.
(A) E...
(A) Expression heatmap of upregulated genes in highly (red) versus weakly/mildly (blue) bone-metastatic A549-derivative cell lines. (B and C) IL-20RB protein (B) and mRNA levels (C) in A549-derivative cell lines. (D–K) Analysis of IL20RB expression in an SHTCH lung cancer cohort. IL20RB expression in paired normal and cancer tissues from the same patients (D), in metastatic and nonmetastatic primary lung tumors (E), and in primary lung tumors metastatic to bone or other organs (F). Bone metastasis–free survival (G) and overall survival (H) analyses of the patients according to different IL20RB expression status. Representative images (I) and quantitation (J) of IL-20RB immunostaining in primary lung tumors and bone metastases and in paired lung tumors and bone metastases from the same patients (K). Tumor cells were stained by pan-cytokeratin (CK). Scale bar: 100 μm. P values were obtained by 2-tailed paired (D and K) or unpaired t test (C, E, F, and J) and log-rank test (G and H). Box plots display values of minimum, first quartile, median, third quartile, and maximum. Data are represented as mean ± SD.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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