项目名称: IL-1β调控成纤维细胞糖酵解在口腔白斑发生发展中的作用
项目编号: No.81200787
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学二处
项目作者: 洪筠
作者单位: 中山大学
项目金额: 24万元
中文摘要: 白斑是重要的口腔癌前病变,必须采取有效手段早期干预和逆转其恶性转变。有学者认为,酵解的肿瘤相关性成纤维细胞(CAF)在乳腺癌、前列腺癌等肿瘤发生的早期即以反向Warburg effect促进肿瘤的发生发展,但该机制在口腔白斑癌变中的情况未明。本课题组前期已初步明确:促炎因子IL-1β可能是实验性口腔黏膜白斑上皮细胞恶性转化过程中上皮-间质对话的关键节点;外源IL-1β可上调口腔CAF的有氧糖酵解,提示IL-1β是成纤维细胞糖代谢的重要调控因子。为此,本项目拟通过临床标本、体外三维模型以及实验动物,采用分子生物学、蛋白组学方法,探讨口腔癌变进展过程中成纤维细胞的糖代谢状况以及IL-1β在其中的作用。旨在解决下述关键科学问题:IL-1β如何调控成纤维细胞的有氧糖酵解?如何影响口腔黏膜癌前损害的演变进程?以期进一步丰富和完善口腔黏膜癌前损害的发病机制、为其寻找早期干预靶点提供实验依据。
中文关键词: 肿瘤间质;成纤维细胞;糖酵解;IL-1β;
英文摘要: Leukoplakia is such an important oral premalignant lesions that effective methods must be found to provide early intervention. Glycolytic cancer associated fibroblasts (CAFs) promoted initial carcinogenesis by reverse Warburg effect. But studies in glycolytic CAFs of oral premalignant lesions are limited. Our previous studies had confirmed that proinflammation factor IL-1β was an important nod of crosstalk between epithelial cells and fibroblasts during experimental oral leukoplakia development. We also found IL-1β could upregulated aerobic glycosis of oral CAFs. Thus we thought IL-1β might be a key controler of CAFs metabolic reprogramming. In this study, we try to explore the role of IL-1β in CAFs of oral leukoplakia in clinical samples, 3D culture model in vitro, and experimental animals in vivo by methods of molecular biology and proteomics.Our scientific questions are: how does Il-1β control glycolytic fibroblasts and how to influence oral premalignant lesions development.
英文关键词: tumor microenvironment;fibroblasts;glycolytic;IL-1β;