Extracellular-vesicle-packaged S100A11 from osteosarcoma cells mediates lung premetastatic niche formation by recruiting gMDSCs
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
Affiliations
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; Corresponding author
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; Corresponding author
Summary: 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.
