Abstract
Hepatocellular carcinoma (HCC) is different from other solid tumors because it is commonly associated with the occurrence of intrahepatic metastasis. Additionally, the liver, unlike other organs, is the main site of coagulation and fibrinolytic factor production. Therefore, it was speculated that coagulation and fibrinolytic factors could be associated with intrahepatic metastasis of HCC. Do the coagulation and fibrinolytic systems protect HCC cells against anoikis during infiltration and metastasis? Conversely, do the coagulation and fibrinolytic systems lead to immune escape of HCC cells by affecting the immune microenvironment of patients? The current review aimed to present a number of novel hypotheses for the treatment of HCC by exploring the mechanisms of coagulation and fibrinolytic factors in the regulation of cancer growth.
Highlights
Hepatocellular carcinoma (HCC) is different from other solid tumors because it is commonly associated with the occurrence of intrahepatic metastasis
Tissue factor (TF), which is expressed by tumor cells, can trigger coagulation directly
Mouse models and clinical follow‐up revealed that tissue factor (TF) expression is associated with angiogenesis and invasiveness of HCC [20,21]
Summary
Hepatocyte growth factor (HGF) was demonstrated to promote the invasion of HCC cells by enhancing the levels of uPA and uPAR. Wang et al [48] revealed that berberine could trigger cell apoptosis by generating reactive oxygen species, and could inhibit the migration and invasion of HCC cells This may be associated with the upregulation of PAI‐1, which could decrease the expression levels of cyclooxygenase‐2 (Cox‐2), NF‐κB, uPA and uPAR via inactivation of the p38 and ERK1/2 signaling pathways [48]. A study of TM in 141 patients with HCC who underwent surgery suggested that TM may inhibit tumor cell invasion to the portal vein and prevent intrahepatic metastasis [63]. Several thrombin inhibitors available for clinical treatment, including non‐specific anticoagulants and thrombin‐specific inhibitors, have been demonstrated to inhibit metastasis in experimental models [10]
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