Neutrophil Extracellular Traps in Tumor Metabolism and Microenvironment

Overview

Journal Biomark Res

Publisher Biomed Central

Date 2025 Jan 24

PMID 39849606

Authors

Zhanrui Liu

Yuanyao Dou

Conghua Lu

Rui Han

Yong He

Affiliations

Soon will be listed here.

Abstract

Neutrophil extracellular traps (NETs) are intricate, web-like formations composed of DNA, histones, and antimicrobial proteins, released by neutrophils. These structures participate in a wide array of physiological and pathological activities, including immune rheumatic diseases and damage to target organs. Recently, the connection between NETs and cancer has garnered significant attention. Within the tumor microenvironment and metabolism, NETs exhibit multifaceted roles, such as promoting the proliferation and migration of tumor cells, influencing redox balance, triggering angiogenesis, and driving metabolic reprogramming. This review offers a comprehensive analysis of the link between NETs and tumor metabolism, emphasizing areas that remain underexplored. These include the interaction of NETs with tumor mitochondria, their effect on redox states within tumors, their involvement in metabolic reprogramming, and their contribution to angiogenesis in tumors. Such insights lay a theoretical foundation for a deeper understanding of the role of NETs in cancer development. Moreover, the review also delves into potential therapeutic strategies that target NETs and suggests future research directions, offering new perspectives on the treatment of cancer and other related diseases.

References

Albrengues J, Shields M, Ng D, Park C, Ambrico A, Poindexter M . Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science. 2018; 361(6409). PMC: 6777850. DOI: 10.1126/science.aao4227. View

Rayes R, Mouhanna J, Nicolau I, Bourdeau F, Giannias B, Rousseau S . Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects. JCI Insight. 2019; 5. PMC: 6777835. DOI: 10.1172/jci.insight.128008. View

Han M, Sun H, Zhou Q, Liu J, Hu J, Yuan W . Effects of RNA methylation on Tumor angiogenesis and cancer progression. Mol Cancer. 2023; 22(1):198. PMC: 10698974. DOI: 10.1186/s12943-023-01879-8. View

Hou D, Hu F, Mao Y, Yan L, Zhang Y, Zheng Z . Cationic antimicrobial peptide NRC-03 induces oral squamous cell carcinoma cell apoptosis via CypD-mPTP axis-mediated mitochondrial oxidative stress. Redox Biol. 2022; 54:102355. PMC: 9511698. DOI: 10.1016/j.redox.2022.102355. View

Xia L, Oyang L, Lin J, Tan S, Han Y, Wu N . The cancer metabolic reprogramming and immune response. Mol Cancer. 2021; 20(1):28. PMC: 7863491. DOI: 10.1186/s12943-021-01316-8. View

Yang D, Liu J . Neutrophil Extracellular Traps: A New Player in Cancer Metastasis and Therapeutic Target. J Exp Clin Cancer Res. 2021; 40(1):233. PMC: 8283906. DOI: 10.1186/s13046-021-02013-6. View

Zhang L, Cao Y, Guo X, Wang X, Han X, Kanwore K . Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma. J Zhejiang Univ Sci B. 2023; 24(1):32-49. PMC: 9837376. DOI: 10.1631/jzus.B2200269. View

Lu C, Gao Z, Wu D, Zheng J, Hu C, Huang D . Understanding the dynamics of TKI-induced changes in the tumor immune microenvironment for improved therapeutic effect. J Immunother Cancer. 2024; 12(6). PMC: 11328648. DOI: 10.1136/jitc-2024-009165. View

Kosgodage U, Trindade R, Thompson P, Inal J, Lange S . Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition of Exosome and Microvesicle Release and Enhanced Efficacy of Cancer Chemotherapy. Int J Mol Sci. 2017; 18(5). PMC: 5454920. DOI: 10.3390/ijms18051007. View

10.

Yin Y, Dai H, Sun X, Xi Z, Zhang J, Pan Y . HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation. Clin Transl Med. 2023; 13(6):e1283. PMC: 10230156. DOI: 10.1002/ctm2.1283. View

11.

Chen G, OLeary B, Du J, Carroll R, Steers G, Buettner G . Pharmacologic Ascorbate Radiosensitizes Pancreatic Cancer but Radioprotects Normal Tissue: The Role of Oxidative Stress-Induced Lipid Peroxidation. Antioxidants (Basel). 2024; 13(3. PMC: 10967795. DOI: 10.3390/antiox13030361. View

12.

Wang Y, Li Y, Chen Z, Yuan Y, Su Q, Ye K . GSDMD-dependent neutrophil extracellular traps promote macrophage-to-myofibroblast transition and renal fibrosis in obstructive nephropathy. Cell Death Dis. 2022; 13(8):693. PMC: 9360039. DOI: 10.1038/s41419-022-05138-4. View

13.

Chatterjee R, Chatterjee J . ROS and oncogenesis with special reference to EMT and stemness. Eur J Cell Biol. 2020; 99(2-3):151073. DOI: 10.1016/j.ejcb.2020.151073. View

14.

Schoeps B, Eckfeld C, Prokopchuk O, Bottcher J, Haussler D, Steiger K . TIMP1 Triggers Neutrophil Extracellular Trap Formation in Pancreatic Cancer. Cancer Res. 2021; 81(13):3568-3579. DOI: 10.1158/0008-5472.CAN-20-4125. View

15.

Tatsiy O, McDonald P . Physiological Stimuli Induce PAD4-Dependent, ROS-Independent NETosis, With Early and Late Events Controlled by Discrete Signaling Pathways. Front Immunol. 2018; 9:2036. PMC: 6153332. DOI: 10.3389/fimmu.2018.02036. View

16.

Schedel F, Mayer-Hain S, Pappelbaum K, Metze D, Stock M, Goerge T . Evidence and impact of neutrophil extracellular traps in malignant melanoma. Pigment Cell Melanoma Res. 2019; 33(1):63-73. DOI: 10.1111/pcmr.12818. View

17.

Adrover J, McDowell S, He X, Quail D, Egeblad M . NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps. Cancer Cell. 2023; 41(3):505-526. PMC: 10280682. DOI: 10.1016/j.ccell.2023.02.001. View

18.

Yang K, Wang X, Song C, He Z, Wang R, Xu Y . The role of lipid metabolic reprogramming in tumor microenvironment. Theranostics. 2023; 13(6):1774-1808. PMC: 10091885. DOI: 10.7150/thno.82920. View

19.

Cane S, Barouni R, Fabbi M, Cuozzo J, Fracasso G, Adamo A . Neutralization of NET-associated human ARG1 enhances cancer immunotherapy. Sci Transl Med. 2023; 15(687):eabq6221. DOI: 10.1126/scitranslmed.abq6221. View

20.

Zha C, Meng X, Li L, Mi S, Qian D, Li Z . Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment the HMGB1/RAGE/IL-8 axis. Cancer Biol Med. 2020; 17(1):154-168. PMC: 7142852. DOI: 10.20892/j.issn.2095-3941.2019.0353. View