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A large volume of data indicates that controlling tumor-associated angiogenesis is a promising therapy against cancer. However, angiogenesis is a complex process, little is known about the differential gene expression in the process of normal endothelial cell differentiation toward tumor vascular endothelial cells induced by tumor microenvironment. The aim of this study is to investigate the effect of tumor microenvironment simulated by the supernatant of esophageal squamous cancer cells (KYSE70) on normal endothelial cells (HUVECs) at the whole genome level. The gene expression profile was studied through gene ontology and signal pathway analysis. Compared with the normal HUVECs, a total of 3769 differentially expressed genes in induced HUVECs were detected, including 1609 upregulated genes and 2160 downregulated genes. Moreover, the microarray data analysis showed that 11 significant biological processes and 10 significant signaling pathways changed most, which are associated with angiogenesis and cell differentiation. According to the different expression levels in the microarrays and their functions, four differentially expressed genes involved in tumor angiogenesis and cell differentiation (IL6, VEGFA, S1PR1, TYMP) were selected and analyzed by qRT-PCR. The qRT-PCR results were consistent with the microarray data. Furthermore, we simulated the tumor microenvironment by human esophageal carcinoma tissue homogenate to investigate its effect on HUVECs, the qRT-PCR results indicated that the above genes were highly expressed in HUVECs after induction by esophageal carcinoma tissue homogenate. In conclusion, tumor microenvironment impact on normal endothelial cells differentiated toward tumor vascular endothelial cells, and the selected genes, which are associated with tumor angiogenesis, would be anti-angiogenesis targets against esophageal carcinoma.

The antitumor effect of the human umbilical vein endothelial cell (HUVEC) vaccine has been well documented; however, its anti‑angiogenic effects on human esophageal squamous cell carcinoma (ESCC) have yet to be studied. In the present study, a 'humanized' mouse model was established by transplanting NOD/SCID mice with human peripheral blood mononuclear cells (PBMC). After 4 weeks, the level of cluster of differentiation (CD)‑45+ human T‑lymphocytes in mouse peripheral blood was >0.1%, which indicated that mouse reconstruction and the human immune system transformation had been successful. The humanized mice were used to evaluate the anti‑angiogenic effect of the HUVEC vaccine on human ESCC. After immunization with the HUVEC vaccine for 5 consecutive weeks, the humanized mice were subcutaneously transplanted with EC9706 cells. The results indicated that the HUVEC vaccine reduced the size of human esophageal carcinoma xenografts by suppressing angiogenesis. In addition, the HUVEC‑immunized mice exhibited reduced expression of angiogenesis‑associated antigens (vascular endothelial growth factor receptor 2 and VE‑Cadherin) in the tumor specimens, and increased levels of angiogenesis‑associated antibodies in the serum. Notably, the HUVEC vaccine also increased the infiltration of human T‑lymphocytes into the spleen of humanized mice. In conclusion, the present study demonstrated the anti‑angiogenic effect of the HUVEC vaccine on ESCC in a humanized mouse model, and set an experimental foundation for the application of the HUVEC vaccine in ESCC patients.