A mathematical model for pattern formation of glioma cells outside the tumor spheroid core
A mathematical model for pattern formation of glioma cells outside the tumor spheroid core
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DOI：
10.1016/j.jtbi.2009.06.025
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发表时间：
2009-10-07
影响因子：
2
通讯作者：
Friedman, Avner
中科院分区：
文献类型：
--
作者：
Kim, Yangjin;Lawler, Sean;Friedman, Avner
胶质母细胞瘤是最常见和最具侵袭性的脑癌类型。确诊后的中位生存期约为一年。胶质瘤细胞从核心肿瘤向周围脑组织的侵袭是治疗失败的一个主要原因：这些迁移细胞在手术切除时没有被消除，并导致肿瘤复发。在入侵细胞的数量以及迁移的程度和模式上都存在差异。细胞可以扩散迁移，也可以被视为与主要肿瘤块不同的细胞团。这种聚集性在体外使用3D球体模型的脑胶质瘤侵袭性也很明显。据报道，U87细胞稳定表达成分活性的EGFRvIII突变受体，通常在胶质母细胞瘤中表达。在这种情况下，细胞以簇的形式迁移，而不是以对照野生型U87细胞中看到的放射状模式迁移的单个细胞。已经提出了几个模型来解释不同的迁移方式，但到目前为止，还没有一个模型探索细胞-细胞黏附的重要作用。本文建立了一个包含黏附作用的数学模型，并对细胞迁移的各种模式进行了解释。结果表明，根据粘附性、趋化性和趋化性参数的不同，迁移模式显示出从分支到分散的逐渐转变，正如实验所报道的那样。(C)2009爱思唯尔有限公司。保留所有权利。
Glioblastoma is the most common and the most aggressive type of brain cancer. The median survival time from the time of diagnosis is approximately one year. Invasion of glioma cells from the core tumor into the surrounding brain tissue is a major reason for treatment failure: these migrating cells are not eliminated in surgical resection and cause tumor recurrence. Variations are seen in number of invading cells, and in the extent and patterns of migration. Cells can migrate diffusely and can also be seen as clusters of cells distinct from the main tumor mass. This kind of clustering is also evident in vitro using 3D spheroid models of glioma invasion. This has been reported for U87 cells stably expressing the constitutively active EGFRVIII mutant receptor, often seen expressed in glioblastoma. In this case the cells migrate as clusters rather than as single cells migrating in a radial pattern seen in control wild type U87 cells. Several models have been suggested to explain the different modes of migration, but none of them, so far, has explored the important role of cell-cell adhesion. The present paper develops a mathematical model which includes the role of adhesion and provides an explanation for the various patterns of cell migration. It is shown that, depending on adhesion, haptotactic, and chemotactic parameters, the migration patterns exhibit a gradual shift from branching to dispersion, as has been reported experimentally. (C) 2009 Elsevier Ltd. All rights reserved.