文献类型：期刊文献

英文题名：Spatiotemporal heterogeneity of neutrophil extracellular traps in hepatocellular carcinoma microenvironment and targeted therapy progress

作者：Zheng, Ying[1,2];Jia, Ganggang[1,2];Li, Bin[1];Li, Chuyi[1];Zhang, Jiucong[1,2];Yu, Xiaohui[1,2]

第一作者：Zheng, Ying

通信作者：Zhang, JC[1];Yu, XH[1];Zhang, JC[2];Yu, XH[2]

机构：[1]Gansu Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]940th Hosp Joint Logist Support Force, Chinese Peoples Liberat Army, Lanzhou 730050, Gansu, Peoples R China

第一机构：甘肃中医药大学中西医结合学院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]corresponding author), 940th Hosp Joint Logist Support Force, Chinese Peoples Liberat Army, Lanzhou 730050, Gansu, Peoples R China.|[10735ed249c6606940a33]甘肃中医药大学中西医结合学院;[10735]甘肃中医药大学;

年份：2026

卷号：24

期号：1

外文期刊名：JOURNAL OF TRANSLATIONAL MEDICINE

收录：;Scopus(收录号：2-s2.0-105047327292);WOS:【SCI-EXPANDED(收录号:WOS:001849458700006)】；

基金：This work was supported by High-level Talent Reserve Pool G2 Talent Project of the 940th Hospital of the Logistics Support Force (2024-G2-4), Guidance Plan of the Science and Technology Department of Lanzhou City (2024-9-144), Key R&D Program of Gansu Province (22YF7FA105) and Gansu University of Traditional Chinese Medicine School-Hospital Collaborative Innovation Project General Project (HXLH-XTCX12) and the Key Research and Development Program of Gansu Provinc (22YF7FA105).

语种：英文

外文关键词：Neutrophil extracellular traps; Hepatocellular carcinoma; Spatiotemporal heterogeneity; Targeted therapy

摘要：Background Neutrophil extracellular traps (NETs) form a spatiotemporally heterogeneous defensive architecture within the tumor microenvironment (TME), representing a newly identified multi-dimensional biological barrier system. Particularly in hepatocellular carcinoma (HCC), this system drives the heterogeneous evolution of the TME through the integration of mechanical stress transduction (YAP/TAZ activation) and protease-mediated signaling network remodeling (reconfiguration of intercellular signaling via proteolytic enzymes like MMP9, e.g. the MMP9/TGF-beta axis).Main body The NET-driven heterogeneous evolution of the HCC TME is characterized by region-specific epithelial-mesenchymal transition (EMT) progression, metabolic reprogramming of tumor cells, and the formation of immunosuppressive niches within the TME. These changes collectively reshape the TME's biological properties, alter the energy landscape of tumor cells (a framework describing dynamic metabolic/functional states of tumor cells shaped by microenvironmental cues), and maintain their stem cell properties, ultimately contributing to therapeutic heterogeneity and cross-regional drug resistance. Existing targeted therapeutic strategies against NETs in HCC and their clinical translational potential are analyzed herein.Conclusions This review systematically synthesizes the spatiotemporal heterogeneity of NETs in the HCC microenvironment and their functional roles, providing new insights into HCC treatment.