Hepatic expression of ANG2 RNA in metastatic colorectal cancer
Hepatic expression of ANG2 RNA in metastatic colorectal cancer
复制标题
DOI：
10.1002/hep.20048
复制
发表时间：
2004-02-01
期刊：
影响因子：
13.5
通讯作者：
Monden, M
中科院分区：
文献类型：
--
作者：
Ogawa, M;Yamamoto, H;Monden, M
我们检测了血管生成调节剂血管生成素(Ang)-2基因在结直肠癌肝转移(CRC)中的RNA含量，以探讨该蛋白在转移灶血管生成中的作用。转移性结直肠癌在肿瘤边界有明显的血流和肿瘤血管形成。逆转录聚合酶链式反应显示转移性结直肠癌组织中ANG2RNA含量高于原发结直肠癌组织。用激光捕获显微切割技术对转移灶进行研究发现，从肝交界区到转移灶周边，以及从转移灶周边到转移灶的中间部分，Ang-2的RNA含量逐渐增加，而Ang1的RNA含量没有增加；免疫组织化学分析证实，Ang-2蛋白的表达也相应地逐渐增加。Tie-2是一种血管生成素受体，主要在肝交界区表达，而在转移性结直肠癌中不表达。血管内皮生长因子(VEGF)也表现出与Ang-2相似的表达模式，解剖标本中Ang-2的RNA含量与VEGF的RNA含量呈显著正相关(P=0.002)。Western印迹分析表明，Ang-1、Ang-2、Tie-2和VEGF的表达可能在转录水平上受到调控。从肿瘤周边到中间部的ANG2RNA含量增加，与内皮细胞周围募集的减少相一致。血管内皮细胞周围的支持细胞，提示Ang-2可能在肿瘤血管发育不成熟中起作用。综上所述，目前的研究表明，Ang-2和VEGF可能在促进结直肠癌肝转移中新血管的形成方面起到协同作用。
We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P = .002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial. supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.