ICAM‐1 Activates Platelets and Promotes Endothelial Permeability through VE‐Cadherin after Insufficient Radiofrequency Ablation

作者：Jian Kong, Changyu Yao, Shuying Dong, Shilun Wu, Yangkai Xu, Ke Li, Ji Liang, Qiang Shen, Qi Zhang, Rui Zhan, Hongtu Cui, Changping Zhou, Haigang Niu, Guoming Li, Wenbing Sun, Lemin Zheng · 发表于：Advanced Science · 年份：2021 · DOI：10.1002/advs.202002228 · 被引用次数：54 · 研究领域：Angiogenesis and VEGF in Cancer、Inflammatory Biomarkers in Disease Prognosis、Prostate Cancer Treatment and Research

Abstract Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) often leads to aggressive local recurrence and increased metastasis, and vascular integrity and platelets are implicated in tumor metastasis. However, whether interactions between endothelial cells and platelets induce endothelial permeability in HCC after insufficient RFA remains unclear. Here, significantly increased CD62P‐positive platelets and sP‐selectin in plasma are observed in HCC patients after RFA, and tumor‐associated endothelial cells (TAECs) activate platelets and are susceptible to permeability after heat treatment in the presence of platelets in vitro. In addition, tumors exhibit enhanced vascular permeability after insufficient RFA in mice; heat treatment promotes platelets‐induced endothelial permeability through vascular endothelial (VE)‐cadherin, and ICAM‐1 upregulation in TAECs after heat treatment results in platelet activation and increased endothelial permeability in vitro. Moreover, the binding interaction between upregulated ICAM‐1 and Ezrin downregulates VE‐cadherin expression. Furthermore, platelet depletion or ICAM‐1 inhibition suppresses tumor growth and metastasis after insufficient RFA in an orthotopic tumor mouse model, and vascular permeability decreases in ICAM‐1 −/− mouse tumor after insufficient RFA. The findings suggest that ICAM‐1 activates platelets and promotes endothelial permeability in TAECs through VE‐cadherin after insufficient RFA, and anti‐platelet and anti...