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：
10232305
负责人：
Pamela K Kreeger
金额：
$ 49.63万
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/10232305
关键词：
Adhesions Age Anatomy Anoikis Ascites Biological Biology Biomimetics 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 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 base cancer cell cancer diagnosis experimental study improved in vitro testing in vivo intraperitoneal 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.

高级浆液卵巢癌（HGSOC）的患者经常被诊断出广泛的转移性疾病，预后不良。在HGSOC中，转移主要发生在转染色体蔓延，其中肿瘤细胞从原发性肿瘤脱离，漂浮在腹膜液中，并附着在间皮层上形成新的转移。患者腹水中的肿瘤细胞作为单细胞或多细胞聚集体存在大小与实验球体相似。我们假设单细胞和基于骨料的转移是 HGSOC转换散布中的不同过程。为了检验这一假设，我们将使用基于工程的方法（体外培养系统，多元建模，计算流体动力学）和生物学方法（分子和细胞测定，患者样品的分析，异种移植模型）。这提案利用一个多样化的合作团队，包括工程，生物学和临床专家 HGSOC的介绍。拟议研究的完成将提高人们对调节转染料分布的机制和对未来工作的潜在目标的识别转移性传播。