Angiogenesis of AFP producing gastric carcinoma: correlation with frequent liver metastasis and its inhibition by anti-AFP antibody.
Angiogenesis of AFP producing gastric carcinoma: correlation with frequent liver metastasis and its inhibition by anti-AFP antibody.
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DOI：
10.3892/or.11.4.809
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发表时间：
2004-04
期刊：
影响因子：
4.2
通讯作者：
Yutaka Takahashi;T. Ohta;M. Mai
中科院分区：
文献类型：
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作者：
Yutaka Takahashi;T. Ohta;M. Mai
我们研究了血管生成在甲胎蛋白(AFP)生产型胃癌(APGC)患者中的作用，APGC是众所周知的预后较差且肝转移频繁的患者。用抗甲胎蛋白、第八因子(内皮细胞)和血管内皮生长因子(VEGF)的抗体进行免疫组织化学分析。研究APGC(n=25)和非APGC(n=68)的档案标本。APGC组血管密度和血管内皮生长因子的表达显著高于非APGC组(P<；0.001)。APGC中甲胎蛋白表达与血管密度、血管内皮生长因子表达呈正相关(p<；0.001)。接下来，我们研究了抗AFP抗体对APGC裸鼠移植瘤的影响。在2个APGC系中，治疗组与对照组相比对肿瘤生长有明显的抑制作用(p<；0.01)。在2个APGC株系中，治疗组与非治疗组之间的血清AFP和VEGF水平也有显著差异，但在非APGC系中无显著差异。此外，在两条线路上，治疗组的血管密度明显低于对照组。因此，这些发现表明APGC的生物学行为依赖于血管生成。抗AFP抗体下调血管生成提示AFP本身可能上调血管生成，抗体治疗可能具有抗血管生成、抑制转移，尤其是肝转移的作用。
We studied roles of angiogenesis in patients with alpha-fetoprotein (AFP)-producing gastric carcinoma (APGC), which is well known to have a poor prognosis and frequent liver metastases. Immunohistochemical analyses were conducted using antibodies against alpha-fetoprotein, factor VIII (endothelial cells) and vascular endothelial growth factor (VEGF). Archival specimens of APGC (n=25) and non-APGC (n=68) were studied. Expressions of vessel density and VEGF were significantly higher in APGC than those in non-APGC (p<0.001). There is a correlation among the AFP expression, the vessel density and the VEGF expression in APGC (p<0.001). Next, we studied the effects of anti-AFP antibody on APGC xenotransplanted in nude mice. There is significant inhibition of tumor growth in the treatment groups compared to the control groups in 2 APGC lines (p<0.01). There were also significant differences in serum AFP and VEGF levels between treatment groups and non-treatment groups in 2 APGC lines, but not in a non-APGC line. Moreover, vessel densities of the treatment groups were significantly lower than those of the control groups in the two lines. These findings thus suggest that the biological behavior of APGC is angiogenesis-dependent. Down-regulation of angiogenesis by anti-AFP antibody suggest that AFP itself may up-regulate angiogenesis, and the treatment by antibody could have anti-angiogenic effects, inhibiting metastasis, especially liver metastasis in APGC.