Micek Hannah M, Rosenstock Lauren, Ma Yicheng, Hielsberg Caitlin, Montemorano Lauren, Gari Metti K, Ponik Suzanne M, Kreeger Pamela K
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705, USA.
APL Bioeng. 2023 Feb 28;7(1):016111. doi: 10.1063/5.0132254. eCollection 2023 Mar.
High-grade serous ovarian cancer (HGSOC) metastasizes through transcoelomic spread, with both single cells and spheroids of tumor cells observed in patient ascites. These spheroids may form through single cells that detach and aggregate (Sph-SC) or through collective detachment (Sph-CD). We developed an model to generate and separate Sph-SC from Sph-CD to enable study of Sph-CD in disease progression. -generated Sph-CD and spheroids isolated from ascites were similar in size (mean diameter 51 vs 55 m, p > 0.05) and incorporated multiple ECM proteins. Using the model, nascent protein labeling, and qRT-PCR, we determined that ECM was produced after detachment. As fibronectin plays a key role in many cell adhesion events, we confirmed that inhibiting RGD-based adhesion or fibronectin assembly reduced Sph-CD-mesothelial adhesion strength under shear stress. Our model will enable future studies to determine factors that favor formation of Sph-CD, as well as allow investigators to manipulate Sph-CD to better study their effects on HGSOC progression.
高级别浆液性卵巢癌（HGSOC）通过腹腔播散转移，在患者腹水中可观察到肿瘤细胞的单细胞和球体。这些球体可能通过分离并聚集的单细胞（Sph-SC）或集体分离（Sph-CD）形成。我们开发了一种模型来生成Sph-SC并将其与Sph-CD分离，以便在疾病进展过程中研究Sph-CD。从腹水中分离出的模型生成的Sph-CD和球体在大小上相似（平均直径分别为51和55μm，p>0.05），并包含多种细胞外基质蛋白。使用该模型、新生蛋白标记和qRT-PCR，我们确定细胞外基质是在分离后产生的。由于纤连蛋白在许多细胞黏附事件中起关键作用，我们证实抑制基于RGD的黏附或纤连蛋白组装可降低剪切应力下Sph-CD与间皮的黏附强度。我们的模型将使未来的研究能够确定有利于Sph-CD形成的因素，并使研究人员能够操控Sph-CD，以更好地研究它们对HGSOC进展的影响。
