Quantitative assessment of the role of collagen alterations in ovarian cancer

胶原蛋白改变在卵巢癌中作用的定量评估

基本信息

批准号：
9910060
负责人：
Paul J Campagnola
金额：
$ 44.78万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9910060
关键词：
3-Dimensional Algorithmic Analysis Animals Architecture Benign Biological Biological Markers Biology Biomimetics Carcinoma Cell Proliferation Cells Clinical Collagen Collagen Fiber Data Data Analyses Detection Development Diagnosis Diagnostic Disease Disease remission Etiology Extracellular Matrix Fiber Gene Expression Generations Goals Gold Image In Vitro Lead Lesion Malignant neoplasm of ovary Measures Metabolism Methods Microfabrication Microscope Microscopy Modeling Modification Molecular Monitor Morphology Neoplasm Metastasis Normal tissue morphology Ovarian Ovarian Serous Tumor Ovarian Tissue Pathologic Phenotype Photochemistry Physiological Protein Isoforms Protocols documentation Recurrence Reproducibility Resolution Role Stromal Cells Structure Survival Rate Techniques Technology Testing Three-Dimensional Imaging Tissues Tumor Tissue Up-Regulation Validation base biomaterial compatibility cancer cell cancer seeding cancer subtypes cell motility cell stroma chemotherapeutic agent clinical care efficacy testing experimental study imaging modality imaging system improved in vitro Model in vivo in vivo imaging insight instrument intravital imaging migration new technology noninvasive diagnosis novel ovarian neoplasm peritoneal cancer public health relevance scaffold second harmonic second harmonic generation imaging submicron three-dimensional modeling tool tumor tumor growth tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): Ovarian cancer is most often diagnosed when the disease has already metastasized, while lesions are still below the resolution of conventional imaging modalities. Alterations of the collagen architecture in the extracellular matrix (ECM) have been observed in ovarian cancer and are thought to be a critical step in the initiation and progression of many epithelial carcinomas and we suggest these changes are potential quantitative biomarkers. To study this possibility, we will develop 3D models of the stroma in ovarian cancer to study the role of collagen alterations in disease development and progression. These models will be derived from Second Harmonic Generation (SHG) images of the collagen architecture and fabricated through multiphoton excited (MPE) photochemistry. This fabrication method affords the creation of sub-micron fibers directly from collagen with high fidelity, where the resulting structures are both biocompatible and biomimetic. We have shown that SHG can differentiate ovarian cancer subtypes which represent different diseases with different etiologies. We therefore hypothesize that SHG imaging provides the context to understand the biological relevance of collagen remodeling in the ovarian tumor microenvironment (TME) and thereby inform the creation of biomimetic models to relate collagen alterations and tumor growth. Cancer cell migration and proliferation and gene expression will be studied both in in vitro and in vivo by seeding the scaffolds representing normal and ovarian tumors with cancer cells representing different disease and will decouple the respective roles of cell phenotype and collagen alterations. Intravital imaging will further these studies by correlating tumor growth and collagen alterations with changes in metabolism. We hypothesize these studies will lead to better diagnostics and superior therapies. To achieve these goals we will advance both the SHG imaging and MPE fabrication technologies, where each will inform the other and lead to better insight into ovarian cancer. We propose the following Aims: Aim 1. Develop refined models of ovarian tumors based on SHG image data. Aim 2. Use the models in vitro and in vivo to understand cancer cell-stromal interactions. Aim 3. Develop in vivo SHG imaging system with complete ex vivo capabilities.

描述（由适用提供）：当疾病已经转移时，最常诊断出卵巢癌，而病变仍低于常规成像方式的分辨率。在卵巢癌中观察到了细胞外基质（ECM）中胶原蛋白结构的改变，被认为是许多上皮癌的主动性和进展的关键步骤，我们建议这些变化是潜在的定量生物标志物。为了研究这种可能性，我们将开发卵巢癌基质的3D模型，以研究胶原蛋白改变在疾病发育和进展中的作用。这些模型将源自胶原蛋白结构的第二次谐波生成（SHG）图像，并通过Multiphoton激发（MPE）光化学制造。这种制造方法可直接从胶原蛋白中产生亚微米纤维，而所得结构既具有生物相容性又生物仿生。我们已经表明，SHG可以区分卵巢癌亚型，这些亚型代表具有不同病因的不同疾病。因此，我们假设SHG成像提供了了解卵巢肿瘤微环境（TME）中胶原蛋白重塑的生物学相关性的背景，从而告知了生物模型的创建以相关的胶原蛋白改变和肿瘤的生长。癌细胞迁移，增殖和基因表达将在体外和通过用代表不同疾病的癌细胞代表正常和卵巢肿瘤的支架播种，体内将使细胞表型和胶原蛋白改变的各自作用。插入成像将通过将肿瘤生长和胶原蛋白改变，新陈代谢的变化。我们假设这些研究将导致更好的诊断和出色的疗法。为了实现这些目标，我们将同时推进SHG成像和MPE制造技术，在这些技术中，每个技术都将为彼此提供信息，并可以更好地了解卵巢癌。我们提出以下目的：AIM 1。基于SHG图像数据开发的卵巢肿瘤模型。目标2。在体外和体内使用模型来了解癌症。细胞界相互作用。 AIM 3。开发具有完全离体功能的体内SHG成像系统。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Assessing the roles of collagen fiber morphology and matrix stiffness on ovarian cancer cell migration dynamics using multiphoton fabricated orthogonal image-based models.

DOI：
10.1016/j.actbio.2022.09.037
发表时间：
2022-11
期刊：
Acta biomaterialia
影响因子：
9.7
作者：
通讯作者：

Polarization-resolved second harmonic generation imaging of human ovarian cancer.

DOI：
10.1117/1.jbo.23.6.066501
发表时间：
2018-06
期刊：
Journal of biomedical optics
影响因子：
3.5
作者：
Campbell KR;Chaudhary R;Handel JM;Patankar MS;Campagnola PJ
通讯作者：
Campagnola PJ

Analysis of fibroblast migration dynamics in idiopathic pulmonary fibrosis using image-based scaffolds of the lung extracellular matrix.

使用基于图像的肺细胞外基质支架分析特发性肺纤维化中的成纤维细胞迁移动力学。

DOI：
10.1152/ajplung.00087.2019
发表时间：
2020
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
0
作者：
Tisler,Marisa;Alkmin,Samuel;Chang,Hsin-Yu;Leet,Jon;Bernau,Ksenija;Sandbo,Nathan;Campagnola,PaulJ
通讯作者：
Campagnola,PaulJ

Examining lysyl oxidase-like modulation of collagen architecture in 3D spheroid models of idiopathic pulmonary fibrosis via second-harmonic generation microscopy.