Ang-2 promotes lung cancer metastasis by increasing epithelial-mesenchymal transition

Abstract

Lung cancer is the most common malignant tumor with increasing angiopoietin-2 (Ang-2) and a high rate of metastasis. However, the mechanism of Ang-2 enhancing tumor proliferation and facilitating metastasis remains to be clarified. In this study, Ang-2 expression and its gene transcription on effects of biological behaviors and epithelial-mesenchymal transition (EMT) were investigated in lung cancers. Total incidence of Ang-2 expression in the cancerous tissues was up to 91.8 % (112 of 122) with significantly higher (χ²=103.753, P<0.001) than that in the paracancerous tissues (27.9%, 34 of 122). High Ang-2 expression was closely related to tumor size (χ²=7.883, P=0.005), differentiation degree (χ²=4.554, P=0.033), tumor node metastasis (TNM) staging (χ²=5.039, P=0.025), and 5-year survival rate (χ² =11.220, P<0.001) with significantly shorter than that of cases with low or no Ang-2. Significant difference was found at TNM staging I (χ²=18.881, P<0.001) and not at II (χ²=0.81, P=0.776) or III & IV (χ²=1.845, P=0.174). Over-expression of Ang-2 or Ang-2 mRNA in lung A549 and NCI-H1975 cells were identified among different cell lines. When silencing Ang-2 in A549 cells with specific shRNA-1 transfection, the cell proliferation was significantly inhibited in a time-dependent manner, with up-regulating E-cadherin, down-regulating Vimentin, Twist, and Snail expression, and decreasing invasion and metastasis of cancer cell abilities, suggesting that Ang-2 promote tumor metastasis through increasing EMT, and it could be a potential target for lung cancer therapy.