Tumor growth and calcification in evolving microenvironmental geometries
Tumor growth and calcification in evolving microenvironmental geometries
复制标题
DOI：
10.1016/j.jtbi.2018.12.006
复制
发表时间：
2019-02-21
影响因子：
2
通讯作者：
Lowengrub, John S.
中科院分区：
文献类型：
--
作者：
Chen, Ying;Lowengrub, John S.
在本文中，我们应用Chen和Lowengrub（Tumor growth in complex，evolving microenvironmental geometries：A diffuse domain approach，J. Theor. 361（2014）14-30）来研究可变形基底膜（BM）对受限的导管几何形状中的肿瘤（例如原位导管癌（DCIS））生长的影响。我们使用肿瘤微钙化的连续模型，并研究微钙化以外的肿瘤范围。为了有效地求解控制方程，我们发展了一种稳定的非线性多重网格有限差分方法。进行二维模拟，其中肿瘤细胞和基底膜之间的粘附是变化的。考虑管道半径和膜刚度的变化，也进行了额外的模拟。结果表明，增强的膜变形性促进肿瘤生长和肿瘤钙化。当导管半径小时，细胞-BM粘附弱或当膜轻微变形时，乳房摄影术和病理学肿瘤范围线性相关，如Macklin等人（J. Theor. 301（2012）122-140），该模型不考虑基底膜的可变形性和膜赋予肿瘤细胞的主动力。有趣的是，我们预测，当导管半径较大时，存在强烈的细胞-BM粘附或膜高度变形，乳腺摄影和病理肿瘤的范围反而二次相关。这些模拟可以帮助外科医生测量DCIS手术边缘，同时切除较少的非癌组织，并可以提高术中和术后放疗的靶向。(C)2018爱思唯尔有限公司版权所有。
In this paper, we apply the diffuse domain framework developed in Chen and Lowengrub (Tumor growth in complex, evolving microenvironmental geometries: A diffuse domain approach, J. Theor. Biol. 361 (2014) 14-30) to study the effects of a deformable basement membrane (BM) on the growth of a tumor in a confined, ductal geometry, such as ductal carcinoma in situ (DCIS). We use a continuum model of tumor microcalcification and investigate the tumor extent beyond the microcalcification. In order to solve the governing equations efficiently, we develop a stable nonlinear multigrid finite difference method. Two dimensional simulations are performed where the adhesion between tumor cells and the basement membrane is varied. Additional simulations considering the variation of duct radius and membrane stiffness are also conducted. The results demonstrate that enhanced membrane deformability promotes tumor growth and tumor calcification. When the duct radius is small, the cell-BM adhesion is weak or when the membrane is slightly deformed, the mammographic and pathologic tumor extents are linearly correlated, as predicted by Macklin et al. (J. Theor. Biol. 301 (2012) 122-140) using an agent-based model that does not account for the deformability of the basement membrane and the active forces that the membrane imparts on the tumor cells. Interestingly, we predict that when the duct radius is large, there is strong cell-BM adhesion or the membrane is highly deformed, the extents of the mammographic and pathologic tumors are instead quadratically correlated. The simulations can help surgeons to measure DCIS surgical margins while removing less non-cancerous tissue, and can improve targeting of intra- and post-operative radiotherapy. (C) 2018 Elsevier Ltd. All rights reserved.