AOC3 accelerates lung metastasis of osteosarcoma by recruiting tumor-associated neutrophils, neutrophil extracellular trap formation and tumor vascularization
Luxia Qi,
Tian Gao,
Chujie Bai,
Zhanfei Guo,
Linjing Zhou,
Xiaodong Yang,
Zhengfu Fan,
Guifang Zhang
Affiliations
Luxia Qi
Department of Medical Oncology, Xinxiang Central Hospital, Xinxiang, 453000, China
Tian Gao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, Beijing, 100142, China
Chujie Bai
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, Beijing, 100142, China
Zhanfei Guo
Department of Rheumatology, Xinxiang Central Hospital, Xinxiang, 453000, China
Linjing Zhou
Department of Medical Oncology, Xinxiang Central Hospital, Xinxiang, 453000, China
Xiaodong Yang
Department of Medical Oncology, Xinxiang Central Hospital, Xinxiang, 453000, China
Zhengfu Fan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, Beijing, 100142, China; Corresponding author. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Guifang Zhang
Department of Medical Oncology, Xinxiang Central Hospital, Xinxiang, 453000, China; Corresponding author. Department of Medical Oncology, Xinxiang Central Hospital, No. 56 Jinsui Avenue, Xinxiang, 453000, China.
Osteosarcoma (OS) has strong invasiveness, early metastasis, high drug resistance, and poor prognosis. At present, OS still lacks reliable biomarkers, which makes early diagnosis of OS more difficult. AOC3 is highly expressed in OS and highly correlated with lung metastasis. qRT-PCR could identify mRNA levels of genes. Immunohistochemistry and Western blot assays could detect protein levels. Immunofluorescence and ELISA assays were applied to evaluate the activation of neutrophils. Additionally, transwell and wound healing assays evaluated cell migration and invasion abilities. Tube formation and sphere-forming assays were applied to detect the angiogenesis. C57BL/6 mice were injected with OS cells to establish a xenograft tumor model to observe the lung metastasis of OS. Flow cytometry is used to evaluate the ability of tumor cells to recruit neutrophils. AOC3 was significantly overexpressed in OS, and down-regulation of AOC3 could inhibit OS migration, invasion, and angiogenesis. AOC3 could increase tumor development and lung metastasis of OS in vivo experiments. The promoting effect of AOC3 on tumor lung metastasis was achieved by recruiting tumor neutrophils. Activated NETs could up-regulate the metastatic ability of OS cells. Tumor neovascularization also played a role in metastasis, and AOC3 supported tumor neovascularization. AOC3 accelerates lung metastasis of OS by recruiting tumor-related neutrophils and utilizing NETs and tumor vascularization formation.
