PT  - JOURNAL ARTICLE
AU  - K Sugimachi
AU  - S Tanaka
AU  - K Taguchi
AU  - S Aishima
AU  - M Shimada
AU  - M Tsuneyoshi
TI  - Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma
AID  - 10.1136/jcp.56.11.854
DP  - 2003 Nov 01
TA  - Journal of Clinical Pathology
PG  - 854--860
VI  - 56
IP  - 11
4099  - http://jcp.bmj.com/content/56/11/854.short
4100  - http://jcp.bmj.com/content/56/11/854.full
SO  - J Clin Pathol2003 Nov 01; 56
AB  - Aim: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the hypervascular type of human hepatocellular carcinoma (HCC). To gain a better understanding of the role of the Ang–Tie2 system in HCC the expression of these genes was investigated in a series of human HCCs. Methods: The expression of the angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and 52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang-1, Ang-2, vascular endothelial growth factor (VEGF), and erythropoietin (EPO) expression was investigated in Hep3B cells. Results: Ang-1, rather than Ang-2, was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly differentiated HCCs characterised by high vascularity (p = 0.02), and in tumours with a peliotic change (p = 0.02). Strong expression of Tie2 was seen in tumour vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli upregulated VEGF and EPO, but not Ang-1 or Ang-2. Conclusions: These data support the evidence that the reversal of Ang-1 and Ang-2 expression plays an important role in the angiogenic and dedifferentiation processes in HCC. The hypoxic stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in human HCC cells.