发现并鉴定肿瘤转移起始细胞在食管癌转移中的作用及临床意义

肿瘤转移是造成食管癌患者死亡的主要原因。肿瘤转移起始细胞（MIC）被认为是原发灶肿瘤中具有较强转移能力的细胞亚群，而食管癌中MIC的分子细胞特征及其介导肿瘤转移的调控机制尚不清楚。申请人前期建立了人食管癌裸鼠足底-腘窝淋巴结转移模型，分离出来自原发灶的肿瘤细胞和淋巴结转移灶的高转移潜能肿瘤细胞，通过单细胞测序的初步分析找到疑似食管癌MIC亚群及其标志基因。在此基础上，本课题计划通过生物信息学方法进一步揭示食管癌转移细胞的特征，利用体内外实验分析鉴定从细胞系和临床样本中分离到的食管癌MIC，研究其在肿瘤转移中的作用及分子机制。并通过对大量临床样本的分析，确定MIC及其特异标志物的临床意义，包括与肿瘤转移和预后的相关性。本项目研究将拓展我们对食管癌MIC的特性和肿瘤转移机理的认识，为寻找肿瘤转移特异性标志物及新的药物治疗靶点提供理论基础，具有重要的科学理论及临床应用价值。

Cancer metastasis is the major cause of esophagus cancer mortality. It has been recognized that a rare and unique population of metastasis-initiating cells (MIC) is critical for metastatic progress. However, little research has been done to explore MIC in esophagus cancer, remaining its features and underlying molecular mechanisms unveiled. We have previously established an esophagus cancer foot-pad popliteal lymph node metastasis model in nude mice and isolated highly metastatic tumor cells from metastatic lymph nodes. Through single-cell transcriptome analysis, we have identified a MIC-like cluster and its signature gene set. This project will further 1) investigate molecular characteristics of esophageal cancer metastatic cells using bioinformatics methods. 2) Isolate and identify MIC within cancer cell lines and clinical samples followed by both in vitro and in vivo analyses, in search for unique characteristics and the role of MIC. 3) Evaluate the clinical and prognostic significances of MIC and metastasis-related markers in esophagus cancer patients. Unraveling molecular and cellular hallmarks of MICs will conceivably expand our understanding of tumor metastasis and facilitate the development of novel therapeutic strategies.