Mathematical Biosciences Institute, The Ohio State University, Columbus, 43210, USA.
Bull Math Biol. 2010 Jul;72(5):1029-68. doi: 10.1007/s11538-009-9481-z. Epub 2009 Nov 12.
This paper is concerned with early development of transformed epithelial cells (TECs) in the presence of fibroblasts in the tumor micro-environment. These two types of cells interact by means of cytokines such as transforming growth factor (TGF-beta) and epidermal growth factor (EGF) secreted, respectively, by the TECs and the fibroblasts. As this interaction proceeds, TGF-beta induces fibroblasts to differentiate into myofibroblasts which secrete EGF at a larger rate than fibroblasts. We monitor the entire process in silico, in a setup which mimics experiments in a Tumor Chamber Invasion Assay, where a semi-permeable membrane coated by extracellular matrix (ECM) is placed between two chambers, one containing TECs and another containing fibroblasts. We develop a mathematical model, based on a system of PDEs, that includes the interaction between TECs, fibroblasts, myofibroblasts, TGF-beta, and EGF, and we show how model parameters affect tumor progression. The model is used to generate several hypotheses on how to slow tumor growth and invasion. In an Appendix, it is proved that the mathematical model has a unique global in-time solution.
这篇论文研究了在肿瘤微环境中存在成纤维细胞的情况下，转化上皮细胞（TECs）的早期发育。这两种类型的细胞通过分别由 TEC 和成纤维细胞分泌的细胞因子（如转化生长因子（TGF-β）和表皮生长因子（EGF））相互作用。随着这种相互作用的进行，TGF-β诱导成纤维细胞分化为肌成纤维细胞，这些细胞分泌 EGF 的速度比成纤维细胞快。我们在一个模拟肿瘤室侵袭测定实验的设置中进行了整个过程的计算机模拟，在该实验中，一个涂有细胞外基质（ECM）的半透膜被放置在两个腔室之间，一个腔室含有 TEC，另一个腔室含有成纤维细胞。我们基于一个偏微分方程组（PDEs）系统开发了一个数学模型，其中包括 TEC、成纤维细胞、肌成纤维细胞、TGF-β 和 EGF 之间的相互作用，并展示了模型参数如何影响肿瘤的进展。该模型被用于生成几个关于如何减缓肿瘤生长和侵袭的假设。在附录中，证明了数学模型具有唯一的全局时解。
