裸小鼠人肺癌术后转移模型的建立及动态观察  

Nude mouse model of postoperative metastasis of human lung cancer and dynamic observation

作　　者：刘蕾[1] 姚明[2] 闫明霞[2] 吴海燕[3] 徐冰[2] 孔韩卫[2] 刘志学[1] 

机构地区：[1]上海大学生命科学学院,上海200444 [2]上海市肿瘤研究所实验病理研究室,上海200032 [3]扬州大学兽医学院,扬州225009

出　　处：《肿瘤》2007年第4期265-268,共4页Tumor

基　　金：上海市科学技术委员会攀登计划资助项目(编号:064909001)

摘　　要：目的:建立裸小鼠人肺癌术后转移模型,动态观察肿瘤转移情况,为研究肺癌转移机制和术后抗转移治疗提供动物模型。方法:采用组织块法建立裸小鼠人非小细胞肺癌NCI-H460皮下移植瘤模型。4周后,随机挑选25只裸小鼠作为手术组切除肿瘤组织,建立术后转移模型,其余15只裸小鼠作为对照组。每2周两组各处死5只裸小鼠,动态观察其远处各脏器转移情况。动物明显消瘦时结束实验,并采用免疫组化法检测MMP-2、OPN、CD44v6、CD62等蛋白在转移灶及原发灶的表达情况。结果:对照组裸小鼠10周时所携瘤体严重坏死,并出现明显消瘦,解剖发现各阶段均无转移。手术组裸小鼠于10周、12周各发现1例肺转移(1/5),14周时裸小鼠明显消瘦,肺转移率达100%(5/5),有肉眼明显可见的肺转移结节,其他脏器未见转移。免疫组化结果表明,MMP-2、OPN、CD44v6、CD62、E-cadherin、TIMP-2在肺转移灶内的表达明显高于原发灶,CD54和MMP-9在转移灶内的表达则低于原发灶。结论:本模型模拟了临床肿瘤根除术后发生远处转移的过程,结果提示肺癌转移的发生可能与部分粘附分子的表达异常相关,同时为研究肺癌转移机制和术后抗转移治疗提供了理想的动物模型。Objective：To establish a nude mouse model of postoperative metastasis of human lung cancer and perform dynamic observations, so as to provide a reliable animal model to study the metastatic mechanism and investigate the postoperative anti-metastasis treatment. Methods： Subcutaneous transplanted model of non small cell lung carcinoma （ NSCLC ） NCI-H460 cells was established by tissue explant technique. Four weeks later, 25 nude mice were randomly selected and had tumor resection to establish the postoperative metastasis model. The other 15 nude mice were regarded as control. Then five mice in each group were sacrificed every two weeks to make the dynamic observation of the distant metastasis. The experiments were terminated when the body weight of nude mice were obviously decreased. The expression of the matrixmetalloproteinase-2 （ MMP-2 ）, osteopontin （ OPN ）, CD44v6, and CD62 in metastases and primary lesions were detected by immunohistochemical method. Results：The tumor body had severe necrosis and the body weight of mice had apparently decrease in the control group after 10 weeks. No metastasis was found in each stage. While in the operation group, metastasis was found in one of the five sacrificed nude mice at the 10th and 12th week. The metastasis rate was 20%. The lung metastasis rate reached 100% （ 5/5 ） with apparent visible lung metastatic nodes when the mice were sacrificed at 14 th week. But no metastasis was observed in other organs. Immunohistochemical （IHC） examination showed that the expression of MMP-2, OPN, CD44v6, CD62, E-cadbcrin, and Timp-2 in metastases were markedly higher than that in primary tumor, however the expression of CD54 and MMP-9 in metastases were significantly lower than that in primary tumor. Conclusion：The model simulates the tumor distant metastasis process after clinical operation. The results of IHC indicate that the metastasis might correlate with abnormal expression of some adhesion molecules. It provides a valuable model for studying the metas

关 键 词：癌 非小细胞肺 小鼠 裸 肿瘤转移 免疫组织化学 模型 动物 

分 类 号：R734.2[医药卫生—肿瘤] R730.231.3[医药卫生—临床医学]