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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.

项目摘要本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 22-058. 虽然标准生物学方法如二维、体外细胞培养和体内动物模型被广泛使用，癌症的复杂性需要一个连续的模型，这对研究某些生物学问题是有用的。系统.在这项工作中，我们建议通过采用多种方法为肿瘤组织工程奠定基础。创新的方法，首先表征，然后建立细胞外基质的仿生模型 (ECM)在肿瘤微环境中。ECM是仿生学中的关键元素，对于考虑在癌症的背景下，其中ECM的组成和结构随着癌症的发生而急剧变化。疾病进展。我们将特别关注高级别浆液性卵巢癌（HGSOC），它与以下因素相关：存活率特别差，不到50%。HGSOC起源于输卵管，转移到输卵管，卵巢，然后通过腹膜扩散到器官，如网膜和小肠肠系膜。人们认识到有更多模型可以研究HGSOC，而现有模型还没有检查ECM组成或结构变化的影响。使用最先进的质谱仪，影像技术和彻底的免疫组织化学分析，我们将描述之间的差异在疾病的不同阶段，正常和患病组织的ECM。我们将利用创新包括组织工程和微制造的工程方法， HGSOC背景下的病理生理学，并检查ECM组成变化的影响，细胞行为的架构。通过这些实验结合计算/统计通过分析，我们将确定我们确定的许多变化中哪些是疾病进展的原因。我们开发的模型将对HGSOC的研究和经验教训产生变革性的影响从我们的过程中可以广泛应用于发展病理生理相关的更大目标，所有癌症类型的模型。