Extracellular-vesicle-packaged S100A11 from osteosarcoma cells mediates lung premetastatic niche formation by recruiting gMDSCs.

Feb 12, 2024

Experts: Chuangzhong Deng, Yanyang Xu, Hongmin Chen, Xiaojun Zhu, Lihua Huang, Zhihao Chen, Huaiyuan Xu, Guohui Song, Jinchang Lu, Wenlin Huang, Ranyi Liu, Qinglian Tang, Jin Wang

The premetastatic niche (PMN) contributes to lung-specific metastatic tropism in osteosarcoma. However, the crosstalk between primary tumor cells and lung stromal cells is not clearly defined. Here, we dissect the composition of immune cells in the lung PMN and identify granulocytic myeloid-derived suppressor cell (gMDSC) infiltration as positively associated with immunosuppressive PMN formation and tumor cell colonization. Osteosarcoma-cell-derived extracellular vesicles (EVs) activate lung interstitial macrophages to initiate the influx of gMDSCs via secretion of the chemokine CXCL2. Proteomic profiling of EVs reveals that EV-packaged S100A11 stimulates the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in macrophages by interacting with USP9X. High level of S100A11 expression or circulating gMDSCs correlates with the presentation of lung metastasis and poor prognosis in osteosarcoma patients. In summary, we identify a key role of tumor-derived EVs in lung PMN formation, providing potential strategies for monitoring or preventing lung metastasis in osteosarcoma.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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ABOUT THE EXPERTS

Chuangzhong Deng, Yanyang Xu, Hongmin Chen, Xiaojun Zhu, Lihua Huang, Zhihao Chen, Huaiyuan Xu, Guohui Song, Jinchang Lu, Wenlin Huang, Ranyi Liu, Qinglian Tang, Jin Wang

Chuangzhong Deng

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Yanyang Xu

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Hongmin Chen

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Xiaojun Zhu

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Lihua Huang

State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Administration Department of Nosocomial Infection, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Zhihao Chen

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Huaiyuan Xu

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Guohui Song

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Jinchang Lu

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Wenlin Huang

State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Ranyi Liu

State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Qinglian Tang

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address: tangql@sysucc.org.cn.

Jin Wang

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address: wangjinr@sysucc.org.cn.