Liver ischemia-reperfusion promotes tumor metastasis via neutrophil-endothelial interactions: targeting ICAM1 to prevent metastatic recurrence

作者：Mingming Fan, Xukang Gao, Jianbo Lin, Wei Chen, Zeping Han, Hao Xiao, Chenhao Zhou, Qiongzhu Dong, Shaoqing Liu, Weifeng Tan, Zhicong Zhao, Xiaoni Kong, Min Xu · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07515-x · 被引用次数：1 · 研究领域：Cancer, Lipids, and Metabolism、Cancer, Stress, Anesthesia, and Immune Response、Hepatocellular Carcinoma Treatment and Prognosis

BACKGROUND: Liver ischemia-reperfusion (IR) injury, commonly encountered in liver surgery and transplantation, has been linked to enhanced metastatic potential in hepatic tumors. The mechanisms underlying this process, however, remain poorly understood. METHODS: In this study, we utilized mouse models of hepatocellular carcinoma (HCC) and colorectal cancer (CRC) to investigate the role of liver IR in tumor metastasis. We employed ICAM1 blockade with atorvastatin to assess its impact on tumor progression. The effects of neutrophil depletion and ICAM1 inhibition on tumor metastasis were evaluated through in vivo and in vitro assays, while clinical data from HCC patients were analyzed for correlations with ICAM1 expression and prognosis. RESULTS: Our results demonstrate that liver IR significantly increases liver and lung metastasis, decreases survival, and facilitates tumor cell infiltration through neutrophil-mediated interactions. ICAM1 expression was upregulated in liver endothelial cells following IR, promoting neutrophil adhesion and tumor cell transmigration. Atorvastatin treatment reduced ICAM1 expression, attenuated neutrophil recruitment, and inhibited tumor metastasis in both liver and lung. Clinical analysis showed that high ICAM1 expression in HCC tissues was associated with poor prognosis, increased neutrophil infiltration, and worse overall survival (OS) and recurrence-free survival (RFS). CONCLUSIONS: This study uncovers the critical role of the ICAM1-neutrophil ...