Hu Hai, Zhang Yushan, Ran Yuling, Zhou Zhuan, Yu Long, Lou Jinning, Yang Zhihua
Department of Cell and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, People's Republic of China.
Cancer Lett. 2007 Jul 8;252(1):123-30. doi: 10.1016/j.canlet.2006.12.015. Epub 2007 Feb 5.
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.
目前肿瘤血管生成的体内研究主要依赖于从小鼠移植模型中获得的结果。在本研究中,我们试图评估人肿瘤内皮细胞在不同移植肿瘤模型中形成新血管的潜力。从人食管鳞状细胞癌中分离肿瘤内皮细胞,然后通过抗VEGFR1/2免疫反应和管腔形成试验进行鉴定。将食管癌细胞和肺癌细胞分别与人食管癌内皮细胞(HECECs)皮下接种到裸鼠体内。人脐静脉内皮细胞(HUVECs)也与食管癌细胞共同接种到小鼠体内作为对照。与单独注射食管肿瘤细胞相比,HECECs共同接种显著促进了移植肿瘤的生长。进行抗CD31和抗人CD31免疫组织化学检测移植肿瘤中的微血管,结果显示与未接种HECECs的肿瘤相比,HECECs形成了人源化微血管并显著增加了移植肿瘤中的微血管密度。然而,HUVEC细胞不能促进食管肿瘤生长,HECECs也不能促进肺肿瘤生长。在这两组异种移植瘤中发现的人源化血管很少。这些结果表明,HECECs与食管肿瘤细胞之间的特异性相互作用有助于异种移植瘤中的新血管构建和食管肿瘤生长。