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Figure 5. NETs promote tumor metastasis. (A) The mechanism of epithelial ovarian cancer intraperitoneal implantation. Neutrophils, attracted to the omentum by various chemotactic factors secreted by cancer cells, engage in NETosis, releasing chromatin that ensnares ovarian cancer cells, contributing to the formation of metastatic foci on the omentum; (B) The mechanism behind liver metastasis in breast and colon cancer. NET-DNA interacts with cancer cells by binding to CCDC25, initiating the ILK-β-parvin-RAC1-CDC42 signaling cascade within cancer cells; (C) The mechanism of lung metastasis in breast cancer. Tumor cells release CC, which interacts with PR3 on the neutrophil membrane, leading to neutrophil recruitment and triggering NETosis. Ultimately, this process promotes lung metastasis by degrading TSP-1; (D) The mechanism of EMT induced by NETs in tumor cells. CG stimulation releases IGF-1 from tumor cells, activating IGF-1R and inducing phosphorylation in MCF-7 cells. This activation enhances E-cadherin activity, subsequently stimulating secondary angiogenesis within target organs. Created with BioRender.com (accessed on 30 June 2022). NETs: Neutrophils extracellular traps; DNA: deoxyribonucleic acid; CCDC25: coiled-coil domain containing protein 25; ILK: integrin-linked kinase; RAC1: ras-related C3 botulinum toxin substrate 1; CDC42: cell division control protein 42; CC: cathepsin C; PR3: proteinase 3; TSP-1: thrombospondin-1; EMT: epithelial-mesenchymal transition; CG: cathepsin G; IGF-1: insulin-like growth factor-1; IGF-1R: insulin-like growth factor-1 receptor; MCF-7: Michigan Cancer Foundation-7.