可模拟阶段性肿瘤发生的三维肺癌组织体外构建及其在肺癌发生发展机制与药物筛选研究中的应用

Lung cancer is the most important death causes by malignant tumor. 3D tumor model in vitro is critical for the research of cancer phenotype, aggressiveness and drug resistance. Tumor is dynamically staged remodeled during tumor progression. However, 3D tumor models is currently hardly to mimic the dynamical progression of tumor and their true behavior in vivo. The structure and components of decellularized tumor matrix is tumor specific. So, it is possible for reconstruction of staged tumorigenesis-mimicking in vitro 3D tumors by using the decellularized tumor matrix of different stage. This project intend to explore the conditions and laws for the decellularization of staged lung tumors at first. Then, the components and bio-interfaces of different nanotopography and mechanical properties of staged decellularized tumor matrix will be analyzed by histology and high resolution characterization technique. On this basis, the staged tumorigenesis-mimicking in vitro 3D lung tumors are reconstructed for the research of aggressiveness, metastasis and angiogenesis of lung tumors in different stages as well as the anti-tumor drug screening. This project will provide powerful tools for the research of staged lung tumor progression and anti-tumor drug screening. In addition, this project is valuable for the design and development of new scaffolds in tumor tissue engineering.

肺癌已成为恶性肿瘤首要死亡原因。体外再造三维肿瘤模型对揭示肿瘤发病机制与药物筛选具有重要价值。在体肿瘤的发生发展是阶段性的连续过程，而目前体外三维肿瘤模型距离真实模拟在体肿瘤生物学行为的实际需求仍有很大差距。肿瘤脱细胞基质的结构组成及空间排布具有肿瘤组织特异性，以癌症发生不同阶段的肿瘤脱细胞基质为支架材料有望构建出可模拟阶段性肿瘤发生的三维肿瘤模型。本项目拟首先摸索不同阶段肺癌组织的脱细胞条件与规律，并借助组织学与高分辨率表征技术对肿瘤发生阶段性脱细胞基质的组成、生物界面拓扑结构与力学特征等三维微环境因素进行解析。在此基础上，构建可模拟阶段性肿瘤发生的肺癌三维组织模型，深入研究肺癌发生不同阶段肿瘤的侵袭、转移及血管化的动态变化规律及其对化疗药物的反应性。本项目可为体外研究肺癌发生发展阶段性动态变化规律及药物筛选提供有力的研究模型，同时也为指导肿瘤组织工程中新型支架材料的设计与研发提供依据。