Department of Chemistry and Chemical Biology, Stevens Institute of Technology, 1 Castle Point Terrace, Hoboken, NJ, 07030, USA.
Department of Chemical Engineering, Stevens Institute of Technology, 1 Castle Point Terrace, Hoboken, NJ, 07030, USA.
Adv Biol (Weinh). 2022 Dec;6(12):e2200197. doi: 10.1002/adbi.202200197. Epub 2022 Sep 9.
Ovarian carcinoma (OC) forms outgrowths that extend from the outer surface of an afflicted organ into the peritoneum. OC outgrowth formation is poorly understood due to the limited availability of cell culture models examining the behavior of cells that form outgrowths. Prompted by immunochemical evaluation of extracellular matrix (ECM) components in human tissues, laminin and collagen-rich ECM-reconstituted cell culture models amenable to studies of cell clusters that can form outgrowths are developed. It is demonstrated that ECM promotes outgrowth formation in fallopian tube non-ciliated epithelial cells (FNE) expressing mutant p53 and various OC cell lines. Outgrowths are initiated by cells that underwent outward translocation and retained the ability to intercalate into mesothelial cell monolayers. Electron microscopy, optical coherence tomography, and small amplitude oscillatory shear experiments reveal that increased ECM levels led to increased fibrous network thickness and high shear elasticity of the microenvironment. These physical characteristics are associated with outgrowth suppression. The low ECM microenvironment mimicks the viscoelasticity of malignant peritoneal fluid (ascites) and supports cell proliferation, cell translocation, and outgrowth formation. These results highlight the importance of the ECM microenvironment in modulating OC growth and can provide additional insights into the mode of dissemination of primary and recurrent ovarian tumors.
卵巢癌 (OC) 形成的赘生物从受影响器官的外表面延伸到腹膜。由于缺乏研究形成赘生物的细胞行为的细胞培养模型，OC 赘生物形成的机制仍不清楚。受人类组织中细胞外基质 (ECM) 成分免疫化学评估的启发，开发了适合研究能够形成赘生物的细胞簇的富含层粘连蛋白和胶原蛋白的 ECM 重建细胞培养模型。结果表明，ECM 促进表达突变型 p53 的输卵管非纤毛上皮细胞 (FNE) 和各种 OC 细胞系的赘生物形成。赘生物由经历向外易位并保留与间皮细胞单层插入能力的细胞引发。电子显微镜、光学相干断层扫描和小振幅振荡剪切实验表明，ECM 水平的增加导致纤维网络厚度增加和微环境的高剪切弹性增加。这些物理特性与赘生物抑制有关。低 ECM 微环境模拟恶性腹膜液（腹水）的粘弹性，并支持细胞增殖、细胞易位和赘生物形成。这些结果强调了 ECM 微环境在调节 OC 生长中的重要性，并可为原发性和复发性卵巢肿瘤的扩散模式提供更多的见解。
