Engineered ECM platforms to analyze progression in high grade serous ovarian cancer

工程 ECM 平台可分析高级别浆液性卵巢癌的进展

• 批准号: 10477026
• 负责人: Paul J Campagnola
• 金额: $ 54.31万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477026
• 关键词: Address; Animal Model; Architecture; Biological; Biological Models; Biology; Biomedical Engineering; Biomimetics; Carcinoma in Situ; Cell Culture Techniques; Collaborations; Collagen; Complement; Computer Analysis; Data; Development; Diagnosis; Disease; Disease Progression; Elements; Engineering; Environment; Epithelial Cells; Epithelial cyst; Extracellular Matrix; Fiber; Foundations; Functional disorder; Generations; Goals; Gynecologic Oncologist; Human; Imaging technology; In Vitro; Influentials; Intestines; Investigation; Lesion; Letters; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Mass Spectrum Analysis; Mesentery; Methodology; Methods; Microfabrication; Microfluidics; Modeling; Multivariate Analysis; Neoplasm Metastasis; Omentum; Organ; Ovary; Pathologist; Peritoneum; Phenotype; Photochemistry; Printing; Process; Property; Protocols documentation; Recording of previous events; Role; Serous; Site; Small Intestines; Statistical Data Interpretation; Structure; Survival Rate; System; Testing; Tissue Engineering; Tissues; Tube; Tumor Cell Line; Tumor Cell Migration; Tumor Tissue; Variant; Work; base; cancer prevention; cancer type; cell behavior; design; experimental study; fimbria; high resolution imaging; in vitro Model; in vivo; innovation; insight; malignant breast neoplasm; mass spectrometric imaging; mortality; neoplastic cell; novel; precursor cell; scaffold; second harmonic; second harmonic generation imaging; tool; tumor; tumor microenvironment; tumor progression; two-dimensional

PROJECT SUMMARY While standard biological methods such as two-dimensional, in vitro cell culture and in vivo animal models are useful to examine certain biological questions, the complexity of cancer requires a continuum of model systems. In this work, we propose to create a foundation for tumor tissue engineering by employing multiple innovative methodologies to first characterize and then build biomimetic models of the extracellular matrix (ECM) in the tumor microenvironment. The ECM is a key element in biomimicry, and particularly important to consider in the context of cancer, where the composition and architecture of the ECM change drastically with disease progression. We will specifically focus upon high-grade serous ovarian cancer (HGSOC), which is associated with a particularly poor survival rate of less than 50%. HGSOC originates in the fallopian tube, metastasizes to the ovary, and then disseminates throughout the peritoneum to organs such as the omentum and small bowel mesentery. There is a recognized for additional models to study HGSOC, and the existing models have not examined the impact of variations in ECM composition or structure. Using state-of-the-art mass spectrometry, imaging technologies and thorough immunohistochemical analysis, we will characterize differences between the ECM of normal and diseased tissues across the different stages of disease. We will utilize innovative engineering approaches including tissue engineering and microfabrication to recreate tissue-specific pathophysiology in the context of HGSOC, and examine the impact of variations in ECM composition and architecture on cellular behaviors. Through these experiments in combination with computational/statistical analysis, we will determine which of the many changes that we identify are causative for disease progression. The models we develop will have a transformative impact on the study of HGSOC, and the lessons learned from our process can be applied broadly towards the larger goal of developing pathophysiologically-relevant models of all cancer types.

项目概要 虽然二维、体外细胞培养和体内动物模型等标准生物学方法是 为了研究某些生物学问题，癌症的复杂性需要连续的模型系统。 在这项工作中，我们建议通过采用多种创新技术为肿瘤组织工程奠定基础 首先表征细胞外基质 (ECM) 的方法，然后构建细胞外基质 (ECM) 的仿生模型 肿瘤微环境。 ECM 是仿生学的关键要素，在仿生学中考虑尤为重要。 癌症背景下，ECM 的组成和结构随疾病发生巨大变化 进展。 我们将特别关注高级别浆液性卵巢癌 (HGSOC)，它与 特别差，成活率不足50%。 HGSOC 起源于输卵管，转移至 卵巢，然后通过腹膜播散至大网膜和小肠等器官 肠系膜。有一个公认的额外模型来研究 HGSOC，而现有模型还没有 研究了 ECM 成分或结构变化的影响。使用最先进的质谱分析法， 成像技术和彻底的免疫组织化学分析，我们将表征之间的差异 不同疾病阶段的正常组织和患病组织的 ECM。我们将利用创新工程 包括组织工程和微加工在内的方法来重建组织特异性病理生理学 HGSOC 的背景，并检查 ECM 组成和架构的变化对细胞的影响 行为。通过这些实验结合计算/统计分析，我们将确定 我们确定的众多变化中哪些是导致疾病进展的原因。我们开发的模型将 对 HGSOC 的研究具有变革性影响，并且可以应用从我们的过程中吸取的经验教训 广泛地实现开发所有癌症类型的病理生理学相关模型的更大目标。