COL6A1在去势抵抗性前列腺癌肿瘤微环境中的调控机制研究

项目名称： COL6A1在去势抵抗性前列腺癌肿瘤微环境中的调控机制研究

项目编号： No.81502192

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： 万方宁

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 最新的研究表明肿瘤间质在肿瘤的发生发展中发挥着重要作用，影响着肿瘤的生物学行为。我们的前期工作发现，COL6A1基因编码的VI型胶原成分在前列腺癌肿瘤间质中表达。该基因在全雄阻断处理后的LNCaP细胞中表达水平明显上升。并且COL6A1在去势抵抗性前列腺癌患者组织中的表达量亦明显高于激素敏感性前列腺癌。通过MatInspector软件分析该基因的启动子区域，我们发现该基因的转录可能受雄激素受体（AR）的影响。而目前COL6A1在细胞外基质中所扮演的角色尚未阐明。本课题将在细胞水平及动物模型中研究COL6A1的转录调控及其对下游蛋白的影响和作用机制，为前列腺癌肿瘤微环境研究提供新认识。本研究有助于揭示前列腺癌去势抵抗发生过程中肿瘤微环境的改变对肿瘤生物学行为的影响，为CRPC的诊治提供崭新的思路。

中文关键词： 前列腺肿瘤；去势抵抗；肿瘤微环境；COL6A1

英文摘要： Recently studies demonstrated that tumor stroma plays an important role in tumori genesis and progression.Tumor stroma can interact with tumor cells that matters a lot in tumor biological behaviors. Our previous study suggested that COL6A1 gene encoded type VI collagen existed in prostate tumor stroma. COL6A1 upregulated in LNCaP cells treated with whole androgen blockade.The expression level of COL6A1 was also higher in castration resistance than androgen sensitive prostate cancer tissues. We further discovered that AR binding site were existed in promoter region of COL6A1 gene. However, the role which COL6A1 played in extracellular matrix were still unclear. Our study aims to elucidate the regulation and the interaction proteins of COL6A1 both in vitro and in vivo to provide new knowledge for tumor microenvironment research of prostate cancer. Our project may improve our understanding of the role tumor stroma played during prostate cancer progression into CRPC and provide new approaches for the prevention and management of CRPC. 

英文关键词： Prostate cancer;castration resistance;Tumor microenvironment;COL6A1