血管及淋巴管生成相关基因表达与肿瘤转移率和转移途径的比较分析  

The relationship between angiogenesis and lymphangiogenesis-related genes expressions and tumor metastases

作　　者：王丰[1] 韦芳[1] 陈霞芳[1] 田毓华[1] 易苗英[1] 谢匡成[1] 黄倩[1] 

机构地区：[1]上海交通大学附属第一人民医院中心实验室,上海200080

出　　处：《肿瘤》2008年第8期635-639,共5页Tumor

基　　金：上海市卫生局百人计划(编号:99BR006);国家自然科学基金杰出青年项目(编号:30325043);国家重点基础研究计划(编号:2004CB518804);上海市青年科技启明星计划(编号:04QMX1417)

摘　　要：目的：研究促进血管及淋巴管生成因子——血管内皮生长因子（vascular endothelial growth factor，VEGF）-A、-C、-D表达水平与肿瘤转移率及转移途径的关系，探讨其在肿瘤转移方面所起的作用，以及是否可作为判断肿瘤转移和预后的指标。方法：建立2种小鼠和4种人的肿瘤动物模型，观察肺、肝及腹股沟、腋下、髂血管和腹主动脉旁淋巴结大小及肿瘤转移情况。实时荧光定量．PCR（real—time fluorogentic quantitative PCR，RFQ—PCR）检测体外培养的肿瘤细胞及小鼠体内生长的肿瘤组织内VEGF—A、-C、-D及血管内皮生长因子受体（vascular endothelial growth factor receptor，VEGFR）-2、-3和淋巴管内皮细胞标志物——淋巴内皮细胞透明质酸受体-1（lymphatic vessel endothelial HA receptor—1，LYVE—1）的表达水平。结果：2种小鼠和4种人的肿瘤动物模型中61％～100％出现了肺转移，16％～100％出现了肝转移，2种小鼠肿瘤动物模型中26％～100％出现了淋巴结转移。结果表明，VEGF—A在肿瘤组织中表达量的增加将伴随着更高的肝、肺转移率。肿瘤组织中VEGF—C的表达水平与肿瘤的淋巴转移存在相关性，但VEGF—D表达水平增加与肿瘤淋巴结转移的发生率并不平行。结论：VEGF—A表达水平与肿瘤血道转移关系密切，VEGF—C在肿瘤淋巴结转移中起重要作用。Objective： Since VEGF-A,C,D and their receptors had been identified to be associated with angiogenesis and lymphangiogenesis, the purpose of this study consists in ： （ 1 ） to evaluate the relationship between VEGF-A, C, D and their receptor expression in tumor cells or tissues and tumor metastasis rate and path ; （2） to explore whether VEGF-A, C or D can be used as parameters for predicting tumor metastasis. Methods： Two allograft and four human xenograft mouse subcutaneous tumor models were established to observe the tumor metastasis. Vascular-path metastasis was confirmed by tumor metastasis in the lung, liver and lymphatic-path metastasis was identified by tumor metastasis in lymph nodes. VEGF-A, C, D and their receptor VEGFR-2, VEGFR-3 and lymphatic endothelium marker, LYVE-1, in tumor cells and tumor tissues were detected by real-time RT-PCR and then correlated with tumor metastasis rate and path. Results： Among the six tumor models, the most common metastases took place in the lung and liver, accounting for 61% - 100% and 16%-100%, respectively. The lymph node metastases were observed in two allograft mouse subcutaneous tumor models. Higher VEGF-A expression level was accompanied with more metastases in the lung and liver and more VEGF-C expression was also correlated with lymph node metastasis, but no correlation between VEGF-D and lymphatic metastasis was observed. Conclusion： VEGF-A plays a pivotal role in tumor vascular-path metastasis and VEGF-C is important to tumor lymphatic-path metastasis.

关 键 词：肿瘤转移 血管生成 病理性 淋巴管生成 基因表达 

分 类 号：R730.231[医药卫生—肿瘤]