使用多尺度数学模型探索上皮-间质转化在卵巢癌进展中的作用。

Exploring the role of EMT in ovarian cancer progression using a multiscale mathematical model.

作者信息

Oliver Samuel, Williams Michael, Jolly Mohit Kumar, Gonzalez Deyarina, Powathil Gibin

机构信息

Department of Mathematics, Swansea University, Swansea, UK.

Department of Biomedical Sciences, Swansea University, Swansea, UK.

出版信息

NPJ Syst Biol Appl. 2025 Apr 17;11(1):36. doi: 10.1038/s41540-025-00508-y.

Abstract

Epithelial-to-mesenchymal transition (EMT) plays a key role in the progression of cancer tumours, significantly reducing the success of treatment. EMT occurs when a cell undergoes phenotypical changes, resulting in enhanced drug resistance, higher cell plasticity, and increased metastatic abilities. Here, we employ a 3D agent-based multiscale modelling framework using PhysiCell to explore the role of EMT over time in two cell lines, OVCAR-3 and SKOV-3. This approach allows us to investigate the spatiotemporal progression of ovarian cancer and the impacts of the conditions in the microenvironment. OVCAR-3 and SKOV-3 cell lines possess highly contrasting tumour layouts, allowing a wide range of different tumour dynamics and morphologies to be tested and studied. Along with performing sensitivity analysis on the model, simulation results capture the biological observations and trends seen in tumour growth and development, thus helping to obtain further insights into OVCAR-3 and SKOV-3 cell line dynamics.

摘要

上皮-间质转化(EMT)在癌症肿瘤进展中起关键作用,显著降低治疗成功率。当细胞发生表型变化时会发生EMT,从而导致耐药性增强、细胞可塑性提高和转移能力增加。在此,我们使用基于代理的3D多尺度建模框架并借助PhysiCell来探究EMT在两种细胞系(OVCAR-3和SKOV-3)中随时间的作用。这种方法使我们能够研究卵巢癌的时空进展以及微环境条件的影响。OVCAR-3和SKOV-3细胞系具有高度不同的肿瘤布局,从而能够测试和研究广泛的不同肿瘤动态和形态。除了对模型进行敏感性分析外,模拟结果还捕捉到了肿瘤生长和发展中观察到的生物学现象和趋势,从而有助于进一步深入了解OVCAR-3和SKOV-3细胞系的动态变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f907/12006308/3bb7f87f5070/41540_2025_508_Fig1_HTML.jpg

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