Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma

Mol Med Rep. 2016 Aug;14(2):1721-5. doi: 10.3892/mmr.2016.5418. Epub 2016 Jun 21.

Abstract

Previous studies have determined that activated hepatic stellate cells (aHSCs) promote the progression of hepatocellular carcinoma (HCC) by increasing angiogenesis in cancerous tissues. In addition, angiopoietin 1 (Ang‑1) has been reported to be involved in tumor growth and metastasis via the promotion of angiogenesis. It remains unclear whether aHSCs and Ang‑1 are involved in the angiogenesis in HCC. A total of 25 HCC and tumor‑adjacent tissues, and 21 normal liver tissues were used in the present study. Immunohistochemistry (IHC) was used to detect the expression of Ang‑1 and α smooth muscle actin (α‑SMA). The expression of CD34 was also analyzed using IHC to evaluate the microvessel density (MVD). The protein expression levels of Ang‑1 were evaluated using western blot analysis. The association between aHSC, Ang‑1 and angiogenesis was determined using Spearman's rank correlation coefficient. The present study determined that the expression of α‑SMA, Ang‑1 and MVD (CD34) was significantly higher in the HCC tissues when compared with tumor‑adjacent tissues and normal liver tissues. Spearman's rank analysis identified a positive correlation between the expression of α‑SMA, Ang‑1 and CD34. This suggests that α‑SMA‑positive aHSCs promoted angiogenesis by expressing Ang‑1, resulting in the proliferation and metastasis of HCC.

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism*
  • Antigens, CD34 / metabolism
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression
  • Hepatic Stellate Cells / metabolism*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Angiopoietin-1
  • Antigens, CD34
  • Biomarkers, Tumor