胰腺癌分泌的exosomes教育BMDCs致预转移小生境在胰腺癌肝转移作用中的分子机制

项目名称： 胰腺癌分泌的exosomes教育BMDCs致预转移小生境在胰腺癌肝转移作用中的分子机制

项目编号： No.81502505

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 余泽前

作者单位： 东南大学

项目金额： 16.5万元

中文摘要： 胰腺癌肝转移是影响胰腺癌患者预后的重要因素。Exosomes是多种活细胞分泌的小囊泡体, 并能将其携带的与来源细胞功能相关的蛋白质等生物活性分子传递给受体细胞而发挥生物学作用。目前认为exosomes是影响肿瘤进展和转移的主要原因之一。本研究从胰腺癌细胞分泌的exosomes传递肝转移相关蛋白/癌蛋白“教育”并动员骨髓衍生细胞（BMDCs）形成“预转移小生境”角度入手，提取不同肝转移潜能的小鼠胰腺癌细胞株分泌的exosomes，并采用iTRAQ定量蛋白质组学对exosomes进行比较蛋白质组学分析，筛选获得肝转移相关蛋白/癌蛋白。通过建立小鼠胰腺癌原位移植瘤转移模型并采用各种分子生物学手段，阐明胰腺癌分泌的exosomes致预转移小生境形成并引起定向肝转移发生的细胞及分子机制。为通过干预胰腺癌细胞分泌的exosomes来治疗胰腺癌肝转移提供新的靶点，使防治胰腺癌肝转移成为可能。

中文关键词： 胰腺癌；预转移小生境；；外泌体；骨髓衍生细胞

英文摘要： The liver metastasis is an important factor affecting the prognosis of patientswith pancreatic cancer. Exosomes are vesicles secreted by a variety of livingcells. They can horizontal transfer a variety of biologically active molecules like proteins to the receptor cells and play a biological role.Exosomes are currently considered as one of the main contributors to tumor progression and metastasis.In this research,we study the pancreatic cancer derived exosomes horizontal transfer of liver metastasis-associated protein/oncoprotein educate and mobilize bone marrow-derived cells (BMDCs) to form the pre-metastatic niche.We ues the low temperature ultra-high-speed centrifugation and density gradient centrifugation to extract the the pancreatic cancer derived exosomes from the same parent, same genetic background but with different metastatic potential of the mouse pancreatic cancer cell lines.Then we use the iTRAQ quantitative proteomics. analysis of two pancreatic cancer cells derived exosomes.And we can acquire the liver metastasis-associated protein/oncoprotein.Through the surgical orthotopic transplantation tumor metastasis model and various means of molecular biology, we can clarify the cellular and molecular mechanisms of directed liver metastases by pancreatic cancer cells derived exosomes which cause the formation of the pre-metastatic niche. So we can provides a new target for the treatment of pancreatic cancer liver metastases through intervention exosomes secreted by tumor cells and host interactions.Then the prevention and treatment of pancreatic cancer liver metastases will become possible.

英文关键词： pancreatic cancer;pre-metastatic nich;exosomes;bone marrow-derived cells