Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis
Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis
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DOI：
10.3892/ijo.2012.1333
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发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Naito, Zenya
中科院分区：
文献类型：
--
作者：
Yamahatsu, Kazuya;Matsuda, Yoko;Naito, Zenya
据报道，VI类中间丝蛋白巢蛋白是各种组织中的祖细胞标志物。在本研究中，我们分析了巢蛋白在胰腺导管腺癌血管生成中的表达和作用，并确定巢蛋白是否是使用基因沉默策略抑制肿瘤血管生成的潜在靶点。巢蛋白表达仅在小血管中检测到，而CD34，CD31和因子VIII也在PDAC的大血管中表达。巢蛋白阳性血管的数量约为CD34阳性血管数量的20%，巢蛋白阳性血管的平均尺寸约为CD34阳性血管的75%。Nestin阳性血管的PCNA标记指数高于CD34阳性血管和Nestin阴性血管。通过使用靶向巢蛋白转录物的siRNA减少巢蛋白表达抑制血管内皮细胞系的生长，但在细胞运动性方面没有差异。在异种移植模型中，给予靶向小鼠巢蛋白的siRNA抑制了裸鼠皮下人胰腺癌细胞的生长。结论：巢蛋白在胰腺癌组织中表达于增生的小血管中，可能是胰腺导管腺癌组织中血管生成的有用标志物。此外，巢蛋白是一个潜在的新的治疗靶点，在胰腺癌，以抑制肿瘤血管生成。
The class VI intermediate filament protein, nestin is reported to be a progenitor cell marker in various tissues. In the present study, we analyzed the expression and roles of nestin in angiogenesis of pancreatic ductal adenocarcinomas, and determined whether nestin is a potential target for inhibiting tumor angiogenesis using a gene silencing strategy. Nestin expression was detected only in small vessels, whereas CD34, CD31 and factor VIII were also expressed in large-sized blood vessels in PDAC. The number of nestin-positive vessels was approximately 20% the number of CD34-positive vessels, and the average dimension of nestin-positive vessels was approximately 75% that of CD34-positive vessels. The PCNA labeling indices of nestin-positive vessels were higher than those of CD34-positive vessels and nestin-negative 'vessels. Reducing nestin expression by use of siRNA targeting nestin transcripts inhibited growth of the vascular endothelial cell lines, but there was no difference in cell motility. In xenograft models, administration of siRNA targeting mouse-nestin suppressed subcutaneous human pancreatic cancer cell growth in nude mice. In conclusion, nestin was expressed in small proliferating blood vessels in pancreatic cancer tissues and may be a useful marker of angiogenesis in pancreatic ductal adenocarcinoma tissues. Furthermore, nestin is a potential novel therapeutic target in pancreatic cancers to inhibit tumor angiogenesis.