科学网基金客服电话
010-62580792
联系我们

国家自然科学基金项目查询

Notch信号通路在ALDH1+/Musashi+胆囊癌干细胞中功能研究

批准号81472738 学科分类肿瘤干细胞 ( H1607 )
项目负责人杨竹林 负责人职称研究员 依托单位中南大学
资助金额70.00
万元
项目类别面上项目 研究期限2015 年 01 月 01 日 至
2018 年 12 月 31 日
中文主题词C10_胆囊、胆道肿瘤;癌干细胞;乙醛脱氢酶-1;Musashi-1;Notch信号通路
英文主题词gallbladder carcinoma;cancer stem cell;ALDH-1;Musashi-1;Notch signaling pathway

摘要

中文摘要 胆囊癌是较常见的恶性消化系统原发肿瘤,发病和转移机制有待研究。肿瘤干细胞为肿瘤组织中仅有极少数具有成瘤潜能的细胞,具有自我更新和增殖等干细胞特性。前期研究发现肿瘤干细胞分子标志物ALDH-1、Musashi-1表达水平与胆囊癌的病理分期和病人预后相关。流式细胞分选获得原代人胆囊癌细胞,并能体外稳定传代,初步体外体内试验证实分选获得的该细胞亚群具有肿瘤干细胞特性。初步机制研究发现Notch信号通路可能在胆囊腺癌肿瘤干细胞生物学功能中扮演重要角色。本项目应用胆囊腺癌肿瘤干细胞为模型,深入研究Notch信号通路对干性维持与自我更新,细胞增殖、侵袭、迁移能力及体外成瘤能力的功能影响。研究内容可望阐明ALDH-1和Musashi-1可作为胆囊癌中CSCs标记物以及其分子机制,发现潜在的治疗靶标和诊断的生物标志物,有望为临床诊断和治疗提供新策略和方法。
英文摘要 Gallbladder cancer is common primary malignant tumor of the digestive system. The full understanding of incidence and metastasis mechanisms is largely lacking. Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Our previous studies found that ALDH-1, Musashi-1 may serve as markers of cancer stem cells and its exprssion levels higly correlated with gallbladder cancer staging and patient prognosis. Human primary gallbladder cancer cells were sorted by Flow cytometry and can be cultured, passaged in vitro. The ALDH1+ subpopulations were confirmed maintainance of stem cell properties both in vitro and in vivo. A preliminary study shown that Notch signaling mechanisms may play an important role in gallbladder adenocarcinoma tumor stem cell. In current project, we will use gallbladder adenocarcinoma cancer stem cells as model to in-depth study how Notch signaling pathway regulating CSCs self-renewal , cell proliferation, invasion and migration in vitro and in vivo. By carring out this project, we will finally figure out ALDH1+/Musashi+ can be used as markers of gallbladder cancer CSCs and their molecular mechanisms , suggesting the potential therapeutic targets and diagnostic biomarkers for clinical diagnosis and treatment of gallbladder cancer.
结题摘要

成果

序号 标题 类型 作者

  • Copyright @ 2007-
  • 中国科学报社
  • All Rights Reserved
  • 地址:北京市海淀区中关村南一条乙三号 电话:010-62580783