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

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‐ICAM‐1 therapy can be used to prevent progression of HCC after insufficient RFA.

Graphene-containing metal–organic framework nanocomposites for enhanced microwave ablation of salivary adenoid cystic carcinoma

“…45,46 (2) Activation of tumor-derived endothelial cells and platelets are implicated in cancer metastasis after insufficient thermal ablation, which could directly or indirectly cause angiogenesis and hypoxia. 11,18,19,47,48 J. Kong et al reported that insufficient RFA promoted endothelial permeability and activated platelets in tumors. 18 Besides, activation of platelets could promote the formation of neovascularization as well as thrombosis.…”

“…11,18,19,47,48 J. Kong et al reported that insufficient RFA promoted endothelial permeability and activated platelets in tumors. 18 Besides, activation of platelets could promote the formation of neovascularization as well as thrombosis. Z. Chen observed high expressions of VEGF and CD31 in tumors in the MW alone treated group.…”

“…Accumulating evidence has shown that high expressions of VEGF and CD31 and elevation of HIFs were observed after insufficient MW ablation 11–13 and insufficient radiofrequency ablation (RFA). 14–19 Inhibition of tumor recurrence following MW ablation remains a challenge in clinic, as evidenced by three-year clinical postablation recurrence data, 20 which threatened the prognosis and lifetime of patients with cancer. Hence, MW ablation has been rarely applied in treating head and neck tumors in recent years.…”

Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma

“…Theoretically, genetic changes occur in the cancer cells around the ablation site when cells are subjected to thermal stimulation, and the cancer cells of incomplete ablation show more aggressive progression than untreated cells. The previous publications have proven that this experiment can imitate the biological properties similar to residual liver tumor observed clinically [22][23][24][25]. Following another 24-h culture, HepG2 xenografts were removed and immediately protected by RNAsafer Stabilizer Reagent (OMEGA, Guangzhou, China) for RNA-seq detection.…”

Clinical characterization and therapeutic targets of vitamin A in patients with hepatocholangiocarcinoma and coronavirus disease

“…RNA-seq analysis revealed downregulation of the MAPK/ERK pathway through the downstream effectors ICAM1, leading to suppress tumor growth and increase chemosensitivity of liver cancer toward chemotherapy [52]. ICAM1 inhibition could suppresses tumor growth and metastasis [53]. A prospective cohort study of 282 patients with liver disease also demonstrated the association of soluble serum ICAM1 and liver cancer development [54].…”