The Effect Of Twist1 And Vasculogenic Mimicry In Invasion And Metastasis Of Endometrial Carcinoma

Objective: To explore the effect of Twist1 and vasculogenic mimicry(VM) in invasion and metastasis of endometrial carcinoma.Methods:Observed the expression of protein Twist1 and protein VE-cadherin in normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial carcinoma(EEC) by immunohistochemical and histochemical staining, and analysis with clinical pathological factors. Researched the formation of VM structure in normal endometrium, endometrial atypical hyperplasia, and endometrioid endometrial carcinoma(EEC) by CD34 and PAS double staining, and analysis with clinical pathological factors. The human endometrial carcinoma cell line of Ishikawa(ISK cells) were transfectioned by the effective fragment of sh RNA of Twist1 gene, then observed: ① The effect of cell proliferation by experiment of Cell Counting Kit-8(CCK-8); ② The effect of the ability of cell migration and invasion by experiment of Transwell Chambers migration and Transwell Chambers invasion; ③ The expression of protein VE-cadherin was detected by experiment of western blotting.Results: 1.The expression of protein Twist1 in the group EEC was abviously higher than the group of normal endometrium and endometrial atypical hyperplasia(P<0.05). The expression of protein Twist1 in poorly differentiated endometrial cancer was higher than the group of high differentiation(P<0.05). The expression of protein Twist1 in group of muscular infiltration > 1/2 was higher than the group of muscular layer infiltration < 1/2(P<0.05). The expression of protein Twist1 in group which the tumor with lymph node metastasis was higher than that without lymph node metastasis(P<0.05).2. The structure of VM can be detected in 16.94% of endometrial carcinoma specimens,whereas in the sample of normal endometrium, endometrial atypical hyperplasia, it cann’t be detected. The structure of VM in poorly differentiated endometrial cancer was more than high differentiation(P<0.01). The structure of VM in the group of muscular infiltration > 1/2 was more than muscular layer infiltration < 1/2(P<0.01). The structure of VM in group which the tumor with lymph node metastasis was more than that without lymph node metastasis(P<0.01).3. The protein expression of VE-cadherin in the group EEC was higher than the group of normal endometrium, endometrial atypical hyperplasia(P<0.05). The protein expression of VE-cadherin in group muscular infiltration > 1/2 was higher than the group of muscular layer infiltration < 1/2(P<0.05). The protein expression of VE-cadherin in group the tumor with lymph node metastasis was higher than that without lymph node metastasis(P<0.05).4. The protein expression of VE-cadherin in the EEC was positively related with the expression of protein Twist1(r = 0.232, P<0.05) and the formation of VM(r=0.251, P<0.05).5. In the experiment of CCK-8, the proliferation ability of the group which transfectioned by the effective fragment of sh RNA of Twist1 gene was lower than the normal control group and the negative control group(P<0.05).6. In the experiment of Transwell Chambers migration and Transwell Chambers invasion, the ability of migration and invasion in the group which transfectioned by the effective fragment of sh RNA of Twist1 gene was lower than the normal control group and the negative control group(P<0.05).7. The protein expression of VE-cadherin in the group which transfectioned by the effective fragment of sh RNA of Twist1 gene was lower than the normal control group and the negative control group(P<0.05).Conclusions: 1. Twist1, the formation of VM and VE-cadherin play a certain role in promoting the invasion and metastasis of endometrial carcinoma. 2. Down-regulate the expression of Twist1 in endometrial carcinoma cell may effectively inhibit the ability of cell proliferation, migration and invasion. Twist1 mayprovide a new therapeutic target for the treatment of endometrial carcinoma. 3. Twist1 may play a positive regulation in the protein expression of VE-cadherin in endometrial carcinoma, then, play a role in the formation of VM.