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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

基本信息

批准号：
10614850
负责人：
Paul J Campagnola
金额：
$ 5.75万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10614850
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 interest malignant breast neoplasm mass spectrometric imaging mortality neoplastic cell novel precursor cell response scaffold second harmonic second harmonic generation imaging tool tumor tumor microenvironment tumor progression two-dimensional

项目摘要

PROJECT SUMMARY This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 22-058. 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.

项目总结本申请是为了回应被确认为非CA-CA的特殊利益通知(NOSI)而提交的 22-058。而标准的生物学方法，如二维、体外细胞培养和体内动物模型癌症的复杂性对于研究某些生物学问题很有用，它需要一系列连续的模型。系统。在这项工作中，我们建议通过使用多个创新的方法，首先表征并建立细胞外基质的仿生模型 (ECM)在肿瘤微环境中。ECM是生物仿生学中的一个关键元素，尤其对在癌症的背景下，ECM的组成和结构随着疾病的发展。我们将特别关注高级别浆液性卵巢癌(HGSOC)，它与特别差的存活率不到50%。HGSOC起源于输卵管，转移至卵巢，然后通过腹膜扩散到大网膜和小肠等器官肠系膜。对于HGSOC的研究有一个公认的额外的模型，而现有的模型还没有检查了ECM组成或结构变化的影响。使用最先进的质谱仪，成像技术和彻底的免疫组织化学分析，我们将表征不同跨疾病不同阶段的正常组织和病变组织的ECM。我们将利用创新包括组织工程和微制造在内的重建组织特异性的工程方法 HGSOC的病理生理学，并检查ECM组成和变化的影响基于蜂窝行为的体系结构。通过这些实验与计算/统计相结合分析后，我们将确定我们确定的许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的研究和所学到的教训产生革命性的影响从我们的过程中可以广泛地应用于开发与病理生理学相关的更大目标所有癌症类型的模型。