High Expression Of COUP-TF2 In Bladder Cancer And Its Role In Tumor Microenvironment

ObjectionBlood vessels play an indispensable role in the development and progression of tumors.At present,Chicken Ovalbumin Upstream Promoter Transcription Factor 2(COUP-TF2)has been shown to promote the development and metastasis of tumor in various animal models such as pancreatic cancer and breast cancer.The formation of blood vessels in the tumor.But in bladder cancer has not been studied.Therefore,the purpose of our study was to analyze the expression of COUP-TF2 protein in human bladder cancer and evaluate its relationship with the clinicopathological features of the tumor and to study the effect of tumor microenvironment on vascular endothelial cells.Hoping to provide new theories and new targets for the diagnosis and treatment of bladder cancer.MethodsFirst,we collected 35 cases of clinical bladder tissue paraffin specimens,including 27 cases of bladder cancer and 8 cases of bladder normal tissue.In the tissue samples,we used immunohistochemistry IHC to detect the expression of COUP-TF2 protein in tissues and the number of CD34-labeled microvessels in the tissues,and to evaluate the number of microvessels labeled with immunohistochemistry.Second,we also cultured Human umbilical vein endothelial cells(HUVEC)with cultured supernatant of bladder cancer cells and bladder normal cells,respectively.The effects of microenvironment of bladder cancer on HUVEC cells were observed by RT-PCR,WB and CCK-8.Result(1)COUP-TF2 is not expressed in bladder cancer cells and is not expressed in bladder normal epithelial cells.COUP-TF2 express in bladder cancer tissue microenvironment,mainly expressed in vascular endothelial cells,vascular myocytes and interstitial And expressed in the nucleus.(2)COUP-TF2 was strongly expressed in 74%of bladder cancer tissues and weakly expressed in 25%normal tissues of bladder.The expression of COUP-TF2 in bladder cancer and bladder normal tissues was significantly different(P = 0.032<0.05).(3)The expression of COUP-TF2 protein was closely related to the pathological grade and clinical stage of bladder cancer,the difference was statistically significant(P = 0.033,0.024<0.05).And microvessel density(MVD)was closely related to the pathological grade and clinical stage of bladder cancer,which was statistically significant(P = 0.001,0.042<0.05).In addition,the expression of COUP-TFII protein was closely related to the MVD and was positively correlated(P<0.01).(4)HUVEC was cultured with bladder cancer supernatant and bladder normal cell supernatant.COUP-TF2 in bladder supernatant has higher expression at both RNA and protein levels and promotes proliferation of HUVEC.ConclusionCOUP-TF2 is highly expressed in bladder cancer and is low in normal bladder tissue,which is positively correlated with pathological stage and clinical grade.In addition,the expression of COUP-TF2 in bladder cancer is positively correlated with microvessel density,and the supernatant of bladder cancer can lead to higher levels of COUP-TF2 in vascular endothelial cells and promote the proliferation of vascular endothelial cells.This suggests that COUP-TF2 is closely related to both the proliferation of vascular cells in the microenvironment of the bladder cancer and the progression of bladder cancer.So COUP-TFII is likely to participate in the proliferation of vascular endothelial cells to promote the progress of bladder cancer.COUP-TF2 is expected to be a molecular marker for the progression of bladder cancer,providing a new target for future treatment of bladder cancer.