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

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

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 3

Osteoclast-secreted IL-19 primes IL20RB-expressing tumor cells for proliferation in bone.

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Osteoclast-secreted IL-19 primes IL20RB-expressing tumor cells for proli...
(A) Quantification of EdU+ A549 cells with IL20RB overexpression and/or treatment of CM from murine bone marrow–derived osteoclasts (OC) for 24 hours. Representative images are shown on the right. OC CM was mixed with A549 culture medium at a 1:3 ratio. (B) Quantification of EdU+ HBM1 cells with IL20RB knockdown and/or treatment with OC CM for 24 hours. (C–E) Organoid formation of A549 (C), HBM1 (D), and LLC (E) after treatment with OC CM. OC CM was mixed with organoid culture medium at a 1:3 ratio. (F and G) Organoid formation of A549 (F) and HBM1 (G) after treatment with OC CM and/or the IL-19–neutralizing antibody (10 μg/mL). (H) Organoid formation of LLC cells after treatment with recombinant IL-19 protein. (I and J) IL-19 secretion of osteoclasts after treatment with control F12K medium or CM from A549 (I) or HBM1 (J) with or without CSF2 knockdown. Scale bars: 100 μm. P values were obtained by 2-tailed unpaired t test. Data are represented as mean ± SD.