Zheng Shaoping, Weng Zhihong, Zheng Shaojiang, Guo Junli, Huang Fengying, Xie Mingxing
Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2010 Feb;30(1):25-8. doi: 10.1007/s11596-010-0105-5. Epub 2010 Feb 14.
In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein (AF) vaccine in a mouse H22 hepatoma model, tumor volume and survival rate of the mice were studied at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining, and anti-FGFR1 antibody-producing B cells (APBCs) were tested by enzyme-linked immunospot (ELISPOT) assay. Compared with the three control groups, the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group (P<0.05). The number of APBCs in AF-immunized mice (129.6+/-10.9) was more than in controls [6.2+/-1.1 (FGFR1), 6.0+/-1.2 (Ag43) and 5.2+/-1.4 (NS), P<0.01]. Moreover, the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice, but not in control groups. MVD in AF-immunized group was significantly lower than in FGFR1-immunized group, Ag43-immunized group and NS group (10.3+/-3.1 vs 39.4+/-8.6 vs 42.3+/-9.8 and 43.6+/-10.6, P<0.01). These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.
为了在小鼠H22肝癌模型中研究重组Ag43/FGFR1嵌合蛋白(AF)疫苗的抗肿瘤血管生成活性,每隔3天研究小鼠的肿瘤体积和存活率。通过免疫组织化学检测微血管密度(MVD)。通过免疫荧光染色检查肿瘤组织内自身抗体的内皮沉积,并通过酶联免疫斑点(ELISPOT)试验检测产生抗FGFR1抗体的B细胞(APBCs)。与三个对照组相比,AF免疫组的肿瘤体积显著减小,生存时间显著延长(P<0.05)。AF免疫小鼠的APBCs数量(129.6±10.9)多于对照组[6.2±1.1(FGFR1)、6.0±1.2(Ag43)和5.2±1.4(NS),P<0.01]。此外,在AF免疫小鼠的肿瘤组织中发现了自身抗体的内皮沉积,而对照组中未发现。AF免疫组的MVD显著低于FGFR1免疫组、Ag43免疫组和NS组(10.3±3.1对39.4±8.6对42.3±9.8和43.6±10.6,P<0.01)。这些发现表明,AF蛋白疫苗通过产生针对自身FGFR1的自身抗体有效抑制肿瘤血管生成和生长。