Tumor Invasion Optimization by Mesenchymal-Amoeboid Heterogeneity
Tumor Invasion Optimization by Mesenchymal-Amoeboid Heterogeneity
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DOI：
10.1038/srep10622
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发表时间：
2015-05-27
影响因子：
4.6
通讯作者：
Ben-Jacob, Eshel
中科院分区：
文献类型：
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作者：
Hecht, Inbal;Bar-El, Yasmin;Ben-Jacob, Eshel
转移的肿瘤细胞通过周围组织和细胞外基质向血管迁移，以便在远处的器官定植。它们通常在一个密集的环境中移动，里面充满了其他细胞。在这项工作中，我们研究了不同类型的相邻细胞之间的协作效应，它们在有定向线索的迷宫环境中迁移。使用计算机化的模型，我们测量不同间充质/阿米巴比例的细胞到达定义的目标的百分比。间充质细胞的壁降解以及两种类型细胞的运动性都与代谢能量样源水平有关。我们发现，间接合作出现在中层能量中，因为间充质细胞创造了阿米巴所使用的路径。因此，我们希望看到一小部分间充质细胞保持在一个主要是阿米巴人的种群中。我们还研究了细胞之间不同形式的直接相互作用，结果表明，能量依赖的相互作用强度对于间充质和阿米巴的迁移都是最优的。得到的蜂窝团簇大小特征与实验结果一致。因此，我们预测，杂交状态，例如上皮-间充质，应该被用作一种应激反应机制。
Metastasizing tumor cells migrate through the surrounding tissue and extracellular matrix toward the blood vessels, in order to colonize distant organs. They typically move in a dense environment, filled with other cells. In this work we study cooperative effects between neighboring cells of different types, migrating in a maze-like environment with directional cue. Using a computerized model, we measure the percentage of cells that arrive to the defined target, for different mesenchymal/amoeboid ratios. Wall degradation of mesenchymal cells, as well as motility of both types of cells, are coupled to metabolic energy-like resource level. We find that indirect cooperation emerges in mid-level energy, as mesenchymal cells create paths that are used by amoeboids. Therefore, we expect to see a small population of mesenchymals kept in a mostly-amoeboid population. We also study different forms of direct interaction between the cells, and show that energy-dependent interaction strength is optimal for the migration of both mesenchymals and amoeboids. The obtained characteristics of cellular cluster size are in agreement with experimental results. We therefore predict that hybrid states, e.g. epithelial-mesenchymal, should be utilized as a stress-response mechanism.