Human esophageal cancer endothelial cells increase tumor growth by incorporating with mouse endothelium

Abstract

Current in vivo investigations of tumor angiogenesis mainly rely on the results obtained from engrafted models in mice. In the present study, we attempt to assess the potential of human tumor endothelium to form neovasculature in different engrafted tumor models. The tumor endothelial cells were isolated from human esophageal squamous cell carcinoma, and then identified by anti-VEGFR1/2 immunoreactions and tube formation assay. Esophageal and lung cancer cells were subcutaneously inoculated into nude mice with human esophageal cancer endothelial cells (HECECs), respectively. The human umbilical vein endothelial cells (HUVECs) were also co-inoculated into mice with esophageal cancer cells as a control. The engrafted tumor growth was significantly promoted by co-inoculation of HECECs in comparison with injection of esophageal tumor cells alone. Immunohistochemistry of anti-CD31 and anti-huCD31 was performed to detect the micro-vessels in the engrafted tumors which revealed that the HECECs formed humanized micro-vessels and significantly increased the micro-vessel density in engrafted tumors comparing with the tumors without HECECs. However, HUVEC cells could not enhance the esophageal tumor growth and the growth of lung tumors could not be increased by HECECs, either. Few humanized blood vessels were found in these two groups of xenografts. These results suggest that the specific interaction between HECECs and esophageal tumor cells contributes to the neovasculature construction and esophageal tumor growth in xenografts.