Vasculogenic mimicry in hepatocellular carcinoma contributes to portal vein invasion

Abstract

Portal vein invasion (PVI) is common in hepatocellular carcinoma (HCC) and largely contributes to tumor recurrence after radical tumor resection or liver transplantation. Vasculogenic mimicry (VM) was an independent vascular system lined with tumor cells and associated with poor prognosis of HCC. The present study was conducted to evaluate the relationship between VM and portal vein invasion. A total of 44 HCC cases receiving anatomic liver resection were included in the study and were divided into groups with and without PVI. The prevalence of VM in each group was examined by CD34-PAS dual staining. The regulatory molecules of VM formation such as Notch1, Vimentin and matrix metalloproteinases (MMPs) were investigated by immunohistochemical staining. Analysis was performed to explore the association of PVI, VM and the VM regulatory molecules. PVI was found in 40.91% (18/44) cases and VM was found in 38.64% (17/44) cases in total samples. The incidence of VM was 72.22% (13/18) in PVI group while it was 15.38% (4/26) in non-PVI group (P<0.001), VM formation was positively correlated with PVI (r=0.574, P<0.001). The VM forming regulatory molecules such as Notch1, Vimentin, MMP-2 and MMP-9 were found to be correlated with PVI in HCC patients. Taken together, our results suggested that VM formation, alone with its regulatory molecules, is the promoting factor of PVI in hepatocellular carcinoma.

The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial–Mesenchymal Transition

“…Evidence suggests that portal vein invasion (PVI) occurs in the early stage of HCC and is associated with metastasis [2,25,26]. In HCC samples, the Runx2 positive rate in group II was higher than in group I, and highest in group III, which might indicate that Runx2 is associated with HCC cell metastasis.…”

“…In addition, Wang and colleagues found that the overexpression of Galectin-3 upregulated the expression of the Wnt protein, activated β-catenin, and induced EMT [36]. Studies of the relationship between Runx2 and Galectin-3 demonstrated that Runx2 mediated the expression of Galectin-3 in skeletal tissue, human glioma cells, and human pituitary tumor [2,37,38]. We noticed that, in HCC samples, Runx2 expression is related to Galectin-3 expression (χ 2 = 5.92, p = 0.018); furthermore, we examined the Galectin-3 expression level in HepG2 and SMMC7721 cells Runx2 transfected models.…”

“…Surgical resection is the main clinical treatment for HCC. Surgical resection accompanied by liver transplantation improved the disease-free survival in some patients with early stage of HCC, as well as their overall survival [2]. However, the overall prognosis of HCC patients is still unsatisfying.…”

Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour

“…These results indicated a higher number of pseudovessels in ASA+Cl-treated mice without any difference in the number of blood vessels between ASA+Cl-treated and control 4T1 mice. Induction of VM in primary tumours of 4T1+ASA/Cl mice was confirmed by higher expression of VE-cadherin (VE-CAD) and secretory leukocyte protease inhibitor (Slpi) (Figure 3H ) with no change in MMP-9, all reported to be markers of VM [ 24 , 22 , 25 , 26 ]. Blood vessels in primary tumours of 4T1+ASA/Cl group were dysfunctional, as evidenced by low expression of the endothelial isoform of nitric oxide synthase (eNOS) and higher expression of Angiopoetin-2 (Ang-2) (Figure 3H ).…”

B7-H4 overexpression is essential for early hepatocellular carcinoma progression and recurrence

“…HCC is the common malignancy with the most common leading cause of cancer-associated mortality globally, which contributes to the poor prognosis and early intrahepatic and extrahepatic recurrence in HCC patients [ 21 , 22 ]. Although surgical resection accompanied by liver transplantation provides some hope to patients with early stage HCC, the OS of HCC patients is still far from satisfying [ 23 ]. Recently, immunotherapy has become an important and effective complementary approach to conventional HCC treatments [ 24 , 25 ].…”