The Effects Of Angiopoietin-1, -2 And Tie-2 On Angiogenesis In The Primary Gastric Cancer

Background and Objective: Angiopoietins (Ang) is a family of vascular growth factors which is an unique member containning agonist and antagonist. The aim was to explore the effects of Ang-1, -2 and Tie-2 on the progression and angiogenesis in the gastric cancers.Methods: By using semiquantitative RT-PCR, the expression of Ang-1, -2 and Tie-2 mRNA was detected, and by applying immunohistochemistry and image analyzing system, the expression of protein was evaluated in 68 primary gastric cancers and adjacent normal tissues. Microvessel density (MVD) was figured out based on CD34 immunohistochemical staining.Results:1. The expression levels of Ang-1 and Tie-2 in normal tissues were higher than those in gastric cancers, while the expression levels of Ang-2 were opposite.2. The expression levels of Ang-1 mRNA in groups of serosal invasion were higher than those of mucosal and muscular invasion, however, the expression of Tie-2 mRNA was contrary. Expression levels of Tie-2 mRNA in elder people (>60) and in groups of well-differential type of gastric cancers were higher than those in younger (<60) and in groups of poorly differential type, respectively.3. A negative correlation between the expression of Ang-1 protein and Tie-2 mRNA and MVD in gastric cancer was observed (R-0.440 and -0.267, P<0.05 respectively), and the correlation between the expression of Ang-2 mRNA and protein and MVD was positive (R=0.319 and 0.729, P<0.05 respectively).4. The relation of the ratio of Ang-l/Tie-2 mRNA and protein to MVD in gastric cancers was negative (R=-0.262 and -0.40, P<0.05 respectively), however the relation of Ang-2/Tie-2 to MVD was positive (R=0.242 and 0.577, P<0.05 respectively). A negative correlation between the expression of Ang-1 and Ang-2 protein was found (R=0.391,P<0.05), and a positive correlation between the ratio of Ang-2/Ang-l protein expression and MVD in gastric cancers was observed(R=0.739, P<0.05). It was found that MVD in groups of the ratio of Ang-2 mRNA T/N over 1 was higher than those in ratio under 1, by investigating the effects of the ratio of Ang-1 and Ang-2 mRNA T/N on MVD in gastric cancers.Conclusion:Our results demonstrated that the expression of Ang-1, -2 and Tie-2 exist in gastric cancer tissues and their adjacent gastric mucosas and participate the differentiation and progression of gastric cancers. Ang-1 activate the Tie-2 receptor, whereas Ang-2 inhibit Ang-1-induced Tie-2 phosphorylation in the angiogensis, and the ratio of Ang-2/Ang-l was a significant association to MVD in gastric cancers. We also found that, when the expression of Ang-2 is high and Ang-1 is low, the angiogenesis in gastric cancers is promoted, otherwise oppositely. The role of Ang-2 in the influence of Angs/Tie on the angiogenesis is dominant.