Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model

人脐静脉内皮细胞疫苗抑制人源化小鼠食管鳞状细胞癌血管生成

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作者:Hangfan Liu, Jimin Zhao, Yi Yang, Guoguo Jin, Xiaoyan Zhang, Dongyu Wang, Chao Xie, Kangdong Liu, Xinhuan Chen, Xiang Li, Fang Tian, Ziming Dong, Jing Lu

Abstract

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.

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