VEGF及其受体的表达与肝癌的生物学特性关系

目的：通过检测裸鼠肝癌模型中肝癌不同生长时期的病理改变与血管内皮生长因子（VEGF）及其受体（VEGFR）KDR及Flt-1的异常表达，探讨肝癌复发转移与VEGF及其受体间的关系。方法：将裸鼠25只随机分成5组，Ⅰ组为对照组，其余20只原位种植人肝癌细胞，分别于1周、2周、3周、4周作血管造影，取标本切片行HE染色及用免疫组化的方法检测anti-VEGF,anti-KDR及anti-Flt-1的表达。结果：血管造影显示种植后2周组肝脏血管开始有增生及扭曲，3周及4周组血管改变更加明显，各组成瘤率均为100％，光镜下1周组可见瘤细胞散在肝血窦周围，2周组瘤组织聚集成团，3周组，4周组瘤细胞团形态不规则，边界不清，向瘤周浸润，瘤细胞团内可见坏死，1周组瘤细胞VEGF表达成弱阳性，2周组VEGF表达成阳性，3周组及4周组VEGF表达强阳性；正常对照组于种植后1周组肿瘤细胞与周围肝细胞VEGFR表达未见明显差异，种植后2周、3周、4周肿瘤新生儿血管VEGFR表达逐渐增强，肿瘤新生血管内皮细胞的VEGFR着色明显强于瘤周血管内皮细胞，肿瘤细胞亦可见VEGFR染以。结论：多血供的肝癌结节VEGF及其受体表达较强，肿瘤的生长，局部浸润，远处转移与VEGF及其受体密切相关，VEGF首先来源于旁分泌，在后期肿瘤自分泌是VEGF高表达的重要来源，这可能是肝癌阻断血供后，癌灶能存活，复发和转移的重要原因之一。

The relationship between the expression of VEGF and VEGFR and biological characteristics of liver cancer

Objective:To investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) and the recurrence or metastasis of liver tumor. Methods: 25 nude mice were averagely divided into 5 groups including control group and the other 4 treated groups.Human hepatocellular carcinoma was implanted into the liver of the treated group,which was induced into the model of liver cancer in mouse.Then,angiography was performed in the treated groups by the end of 1wk,2wk,3wk and 4wk,respectively.Meanwhile,HE staining of the specimen of the liver cancer in mice was made to measure the expression of VEGF,KDR and Flt 1.Results:After implantation of hepatocellular carcinoma,angiogram showed increased and tortuous vascularities of the liver in model at 2 weeks,and dramatic change of the vascularity at 3 and 4 weeks.All mice in treated groups were found tumor cells.Microscopically,tumor cells were shown around blood sinusoid in 1 week,the tumor cells assembled a mass in 2 weeks.The tumor appeared irregular and the border of the mass was ill defined in 3 and 4 weeks.The expression of VEGF enhanced gradually from 1wk to 4wks.There was no significant difference in the expression of VEGFR between the control group and treated group in 1 week.The expression of VEGFR in the neovascularity of the tumor gradually enhanced from 2 to 4 weeks,and its HE staining appeared more obviously than that of vessel endothelial cells around the tumor.Conclusion:The expressions of VEGF and VEGFR in the hypervascular hepatocellular carcinoma appear obviously.And their expressions may be closely associated with the growth,invasion and distant metastasis of the tumor.