白细胞介素在胃肠癌发生发展中的协作机制

该集成项目主要针对非可控性炎症恶性转化中的白介素细胞因子在胃肠癌症发生发展中的功能及协作信号网络开展研究。拟研究IL-1b及相关炎症小体、IL-6和IL-17在人胃肠肿瘤组织中的表达相关性及其在胃肠肿瘤高危人群中的早期诊断中作用；IL-1b、IL-6和IL-17在胃肠肿瘤发生发展中的功能关联性及作用机制；IL-1b、IL-6和IL-17在胃肠肿瘤发生发展中的动态变化规律；IL-1b、IL-6和IL-17在诱发胃肠上皮细胞恶性转化过程中的协作信号网络。通过整合应用肿瘤学、免疫学、细胞生物学、生化与分子生物学和生物信息学等研究手段，利用临床病人样本，结合小鼠体内疾病模型和细胞体外研究体系，该项目将系统阐明这些白介素细胞因子在胃肠癌发生发展的功能与协作网络，为炎症相关性肿瘤的早期诊断、早期预防和早期治疗提供新的理论基础、新靶点和新策略。

The aim of this integrated grant is to disect the functional signaling network of interleukins in the gastrointestinal tumorigenesis to understand the mechanisms of uncontrolled inflammation in promoting tumor development. The grant is proposed to investigate: 1) The association of the expression levels of IL-1b and related inflammasome, IL-6 and IL-17 in human gastrointestinal tumors, and the potential roles of the cytokines in early diagnosis for the high-risk individuals of gastrointestinal tumors; 2) The functional interactions and mechanisms of IL-1b, IL-6 and IL-17 in the development of gastrointestinal tumors; 3) The dynamic changes of IL-1b, IL-6 and IL-17 in the gastrointestinal tumorigenesis; 4) The cooperational signaling network of IL-1b, IL-6 and IL-17 in promoting malignant transformation of gastrointestinal epithelial cells. Through combining advanced approaches in tumor biology, immunology, cell biology，biochemical and molecular biology, and bioinformatics, analyzing clinical samples, and using in vivo mouse disease models and in vitro cell culture system, this grant will systemically demonstrate the critical roles and cooperational signaling network of these interleukins in the development of gastrointestinal tumors to provide new targets, markers and strategies for early diagnosis, prevention and therapy of inflammation-driven tumors.