子宫平滑肌肉瘤血管内皮细胞综合性基因组特征及治疗靶点分析

Unique tumor endothelial cell isolation technique was used to investigate comprehensive genomic characterization of vascular endothelial cell of uterine leiomyosarcoma. We analyzed normal myometrium, fibroid , and leiomyosarcoma associated endothelial cell RNA from uterus by Gene Microarray. Through qPCR we verified LAMC2 and HOXD10 which was significantly changed gene as candidate for targeting tumor associated endothelial cell. By adenovirus and lentivirus infection technique, we are going to do series cytological and molecular biological investigation; by co-injeciton of tumor associated endothelial cells with leiomyosarcoma tumor cells, we are planning to study their effect in tumor progression by histological analysis; in the end we are trying to develop neutralizing antibody to analyze LAMC2 and HOXD10 effect in tumor angiogenesis. Our study is dedicated to find "Biomarker" of tumor vasculature which can distinguish normal blood vessel and tumor vessel and elucidate the specificity of this biomarker and its mechanism.

本研究利用独特的肿瘤内皮细胞分离技术，采用正常子宫平滑肌、良性子宫肌瘤及子宫平滑肌肉瘤组织中分离出的血管内皮细胞进行基因阵列分析，建立功能相关的基因网络，经qPCR 定量分析后，选取表达量显著变化的LAMC2及HOXD10作为肿瘤内皮细胞靶向治疗的候选基因。本项目计划采用腺病毒转录及基因沉默技术，拟对LAMC2和HOXD10进行一系列细胞学及分子生物学检测；采用平滑肌肉瘤细胞与正常或肿瘤血管内皮共注射技术建立平滑肌肉瘤动物模型，进行组织学检测，分析他们在肿瘤生长过程中的作用；最后选取LAMC2和HOXD10中和抗体在体研究LAMC2及HOXD10 的抗肿瘤血管新生作用。本研究旨在发现区别于正常血管，而特异性表达于肿瘤血管的“标志性”基因，阐明其生物学特异性及作用机制，为平滑肌肉瘤乃致其他肉瘤的基因靶向辅助治疗提供理论和实验基础。