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The role of multi-cellular aggregates vs. individual tumor cells in metastasis of high-grade serous ovarian cancer

多细胞聚集体与单个肿瘤细胞在高级别浆液性卵巢癌转移中的作用

基本信息

批准号：
10553590
负责人：
Pamela K Kreeger
金额：
$ 51.74万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-07 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10553590
关键词：
Adhesions Age Anatomy Anoikis Ascites Biological Biology Biomimetics Cell Aggregation Cell-Cell Adhesion Cells Cellular Assay Clinical Computer Simulation Data Detection Diagnosis Disease Elements Engineering Extracellular Matrix Extracellular Matrix Proteins Future Greater sac of peritoneum In Vitro Individual Integrins Liquid substance Malignant Neoplasms Malignant neoplasm of ovary Mechanics Mesothelial Cell Mesothelium Methods Modeling Molecular Motion Movement Mus Neoplasm Metastasis Ovary Pathologic Pathway interactions Patients Pelvis Peritoneal Peritoneal Fluid Peritoneum Primary Neoplasm Process Prognosis Progression-Free Survivals Quality of life Race Resistance Respiratory Diaphragm Role Sampling Selectins Serous Site Solid Neoplasm Survival Rate System Testing Therapeutic Tissues Variant Work Xenograft Model Xenograft procedure cancer cell cancer diagnosis experimental study improved in vitro testing in vivo intraperitoneal meter mouse model multidisciplinary neoplastic cell palliation patient prognosis patient variability response shear stress simulation surgery outcome tumor tumor growth tumor microenvironment tumor progression

项目摘要

Patients with high-grade serous ovarian cancer (HGSOC) are frequently diagnosed with extensive metastatic disease, resulting in a poor prognosis. In HGSOC, metastasis occurs primarily by transcoelomic spread, where tumor cells detach from the primary tumor, float through the peritoneal fluid, and attach to the mesothelial layer to form new metastases. Tumor cells in patient ascites exist as single cells or in multi-cellular aggregates similar in size to experimental spheroids. We hypothesize that single cell and aggregate-based metastasis are distinct processes in HGSOC transcoelomic spread. To test this hypothesis, we will utilize a combination of engineering-based approaches (in vitro culture systems, multivariate modeling, computational fluid dynamics) and biological methods (molecular and cellular assays, analysis of patient samples, xenograft models). This proposal leverages a diverse, collaborative team that includes experts in engineering, biology, and the clinical presentation of HGSOC. Completion of the proposed studies will result in an improved understanding of mechanisms regulating transcoelomic spread and identification of potential targets for future work to control metastatic spread.

高级别浆液性卵巢癌(HGSOC)患者常被诊断为广泛转移疾病，导致预后不良。在HGSOC中，转移主要通过跨体腔扩散发生，其中肿瘤细胞从原发肿瘤中分离出来，漂浮在腹腔液中，并附着于间皮层。形成新的转移瘤。患者腹水中的肿瘤细胞以单细胞或多细胞聚集体的形式存在。大小与实验中的椭球体相似。我们假设基于单个细胞和聚集的转移是 HGSOC跨体腔体扩散的不同过程。为了验证这一假设，我们将使用以下组合基于工程的方法(体外培养系统、多元建模、计算流体力学) 以及生物学方法(分子和细胞分析、患者样本分析、异种移植模型)。这 Proposal利用了一个多元化、协作的团队，其中包括工程、生物学和临床方面的专家介绍HGSOC。拟议研究的完成将有助于更好地了解跨体腔传播的调控机制和未来工作的潜在控制目标转移性扩散。