CLDN11在胰腺癌神经浸润动物模型中mRNA水平的表达

The Expression of CLDN11 in Animal Model of Pancreatic Caner with Neural Invasion

目的:神经浸润的发生预示胰腺癌预后不良,疼痛的发生与神经浸润密切相关,癌细胞和神经组织间相互作用、连接及粘附可能参与了神经浸润的发生,Claudins作为组成紧密连接的主要成份,在多种肿瘤中有所表达,本实验拟通过观察其成员CLDN11在体内、体外mRNA水平的表达,探讨CLDN11在胰腺癌神经浸润发病机制中的作用,为其诊断及治疗新方法的探索提供一定的实验依据。方法:通过裸鼠坐骨神经周围注射不同人胰腺癌细胞系的方法建立稳定的胰腺癌神经浸润动物模型,成瘤后检测肿瘤组织中CLDN11 mRNA表达水平的差异。同时检测不同人胰腺癌细胞株中CLDN11 mRNA的表达水平的差异。结果:CLDN11在神经侵犯发生率低的肿瘤中的表达高于神经侵犯发生率高的肿瘤,在正常胰腺组织中无表达。CLDN11的mRNA水平在panc-1细胞株中表达高于Capan-2组。结论:经本实验研究发现CLDN11在PNI发生率高的肿瘤组织及高神经浸润能力的细胞株中表达下调,而在PNI发生率低的肿瘤组织及神经浸润能力低的细胞株中高表达,可以得出在神经浸润发生中,CLDN11的表达受到抑制的结论,由此推断如果过表达CLDN11,有可能阻碍PNI的发生及发展;另外,CLDN11表达的下降也可能预示着PNI的发生及进展,因此CLDN11表达的下降可作为PNI发生的预警信号,也可作为胰腺癌基因治疗的靶点,为提高胰腺癌的早期诊断率、改善胰腺癌的预后提供初步的基础实验依据。

Objective： Perineural invasion（PNI） indicates poor prognosis of pancreatic cancer, the presence of pain in pancreatic cancer is associated with PNI. Interactions, connection and adhesion between cancer cells and nerve tissue may be involved in perineural invasion occurred. Claudins contribute to formation of tight junctions, has been found to be altered in several cancers. By observing CLDN11 mRNA expression levels in vitro and in vivo, to explore the role of CLDN11 in pathogenesis of pancreatic cancer with perineural invasion, to provide some experimental basis to earlier diagnosis and explore new treatment. Methods： Established an animal model of neural invasion of pancreatic cancer by using different human pancreatic cancer cells injected around the sciatic nerve of Nude mice. Detecting the different expression levels of CLDN11 mRNA in different tumor tissues and Human pancreatic cancer cell lines.Results： The expression of CLDN11 mRNA in the low incidence of PNI tumors was higher than that of in the high incidence of PNI tumors, no expression in normal pancreatic tissue. The expression of CLDN11 mRNA in Capan-2 was lower than that of in panc-1.Conclusion： CLDN11 expression was low in highly PNI tumors and cell lines compared with low invasive ones. The high expression in low incidence of PNI tumor tissue and low infiltration capacity of cell lines. Come to a conclusion that the expression of CLDN11 was inhibited in PNI. These data suggest that over expression of CLDN11 might obstruct the occurrence and development of PNI. Additionally,Decreased expression of CLDN11 may also indicate the occurrence and progress of PNI. Dropped CLDN11 expression may be as an early warning signal of PNI, it also can be used as target for gene therapy of pancreatic cancer. Our experiments provide a preliminary basis for improving the early diagnosis and prognosis of pancreatic cancer.