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.

项目摘要该申请是为了响应特殊利益通知（NOSI）而提交 22-058。虽然标准的生物学方法，例如二维，体外细胞培养和体内动物模型对于检查某些生物学问题有用，癌症的复杂性需要模型的连续性系统。在这项工作中，我们建议通过使用多个来为肿瘤组织工程创造基础首先要表征创新的方法，然后构建细胞外基质的仿生模型（ECM）在肿瘤微环境中。 ECM是仿生中的关键要素，对于考虑在癌症的背景下，ECM的组成和结构随着疾病进展。我们将特别关注高级浆液卵巢癌（HGSOC），这与尤其是较差的生存率小于50％。 HGSOC起源于输卵管，转移到卵巢，然后在整个腹膜中传播到诸如小肠和小肠等器官肠系膜。有一个公认的其他模型可以研究HGSOC，现有模型尚未检查了ECM组成或结构中变化的影响。使用最先进的质谱法，成像技术和彻底的免疫组织化学分析，我们将表征在疾病的不同阶段，正常组织和患病组织的ECM。我们将利用创新工程方法包括组织工程和微加工，以重新创建组织特异性 HGSOC背景下的病理生理学，并检查ECM组成和有关细胞行为的结构。通过这些实验与计算/统计结合分析，我们将确定我们确定的许多变化中的哪些是疾病进展的原因。我们开发的模型将对HGSOC的研究以及所学的经验教训产生变革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相关的更大目标所有癌症类型的模型。