基于肿瘤微环境与EXOSOME(外排囊泡）的结直肠癌肝转移机制研究

项目名称： 基于肿瘤微环境与EXOSOME(外排囊泡）的结直肠癌肝转移机制研究

项目编号： No.81472666

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郑树

作者单位： 浙江大学

项目金额： 72万元

中文摘要： 结直肠癌（CRC）肝转移是结直肠癌的死亡主因。为阐明CRC易于发生肝转移的特殊现象，基于种子与土壤及转移动力学说，结合国内外的研究与我们工作积累，拟研究：A. 种子研究 ：肿瘤细胞具有不同转移潜能，我们已从有/无肝转移的原发灶中，验证了促转移的骨桥蛋白（OPN）及抑转移的SPARCL1基因，拟对有肝转移小癌灶（T1、T2）与无转移的大癌灶(T3、T4)的基因转录组进一步分折，寻找种子相关基因。B. 微环境研究：应用生物信息学，分析前一部分的表达谱数据，筛选与微环境相关差异表达基因，并验证其功能及机制。C.CRC的外排囊泡（Exosome）研究：通过体内外实验（高/低转移SW620细胞及裸鼠肝转移模型），分离Exosome，验证其前转移Niche诱导肠癌肝转移的潜在机制。本课题预期能进一步揭示CRC肝转移机制，为干预阻断提出新的可实践理论依据。

中文关键词： 外排囊泡；结直肠癌；肿瘤转移

英文摘要： Colorectal cancer (CRC) liver metastases is the leading cause of death for cancer patient. To illustrate a special phenomenon CRC liver metastases , based on the seed and soil and transfer of power doctrine , combined with our previous domestic and international research work, the following studies will be performed: A. seed Study: Cancer cells have different metastastic potential. We tested the primary tumors with/without liver metastasis and verified metastasis-promoting gene osteopontin (OPN) and suppresser gene SPARCL1. We will analyse transcriptome of tumor tissue with liver metastasis(T1, T2) and tumor tissue without metastasis (T3, T4) for seed related genes. B. microenvironment Study: using bioinformatics analysis of previous gene expression data, screening differentially expressed genes associated with microenvironment, and verify its function and mechanism. C.CRC efflux vesicles (Exosome) Study: by in vivo experiments ( high/low metastatic SW620 cells and liver metastasis model in nude mice ) , isolated Exosome, potential mechanisms to verify its former colorectal liver metastases induced shift Niche. The project is expected to reveal the CRC liver metastases mechanism and provide new practical theoretical basis for blocking the proposed intervention.

英文关键词： Exosome;Colorectal Cancer;Metastasis