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

高级别浆液性卵巢癌（HGSOC）患者经常被诊断为广泛转移性卵巢癌。 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上脱落，漂浮在腹膜液中，附着在间皮层上 形成新的转移患者腹水中的肿瘤细胞以单细胞或多细胞聚集体形式存在 大小与实验球体相似。我们假设，单细胞和聚集性转移是 HGSOC跨体腔扩散的不同过程。为了验证这一假设，我们将结合使用 基于工程的方法（体外培养系统，多变量建模，计算流体动力学） 和生物学方法（分子和细胞测定、患者样品分析、异种移植模型）。这 该提案利用了一个多元化的协作团队，其中包括工程、生物学和临床方面的专家， HGSOC的介绍。完成拟议的研究将使人们更好地了解 调节跨体腔传播的机制和确定未来工作的潜在目标， 转移性扩散。

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.