Center for Information Services and High Performance Computing, Technische Universität Dresden, 01062, Dresden, Germany.
Department of Biophysical Chemistry, Institute of Physical Chemistry, Heidelberg University, 69120, Heidelberg, Germany.
Sci Rep. 2017 Aug 23;7(1):9237. doi: 10.1038/s41598-017-09300-3.
During tissue invasion individual tumor cells exhibit two interconvertible migration modes, namely mesenchymal and amoeboid migration. The cellular microenvironment triggers the switch between both modes, thereby allowing adaptation to dynamic conditions. It is, however, unclear if this amoeboid-mesenchymal migration plasticity contributes to a more effective tumor invasion. We address this question with a mathematical model, where the amoeboid-mesenchymal migration plasticity is regulated in response to local extracellular matrix resistance. Our numerical analysis reveals that extracellular matrix structure and presence of a chemotactic gradient are key determinants of the model behavior. Only in complex microenvironments, if the extracellular matrix is highly heterogeneous and a chemotactic gradient directs migration, the amoeboid-mesenchymal migration plasticity allows a more widespread invasion compared to the non-switching amoeboid and mesenchymal modes. Importantly, these specific conditions are characteristic for in vivo tumor invasion. Thus, our study suggests that in vitro systems aiming at unraveling the underlying molecular mechanisms of tumor invasion should take into account the complexity of the microenvironment by considering the combined effects of structural heterogeneities and chemical gradients on cell migration.
在组织浸润过程中，单个肿瘤细胞表现出两种可相互转换的迁移模式，即间质型和阿米巴型迁移。细胞微环境触发两种模式之间的转换，从而允许适应动态条件。然而，目前尚不清楚这种阿米巴-间质迁移可塑性是否有助于更有效的肿瘤浸润。我们通过一个数学模型来解决这个问题，其中阿米巴-间质迁移可塑性是响应局部细胞外基质阻力来调节的。我们的数值分析表明，细胞外基质结构和趋化梯度的存在是模型行为的关键决定因素。只有在复杂的微环境中，如果细胞外基质高度异质且趋化梯度指导迁移，那么与非转换的阿米巴和间质模式相比，阿米巴-间质迁移可塑性允许更广泛的浸润。重要的是，这些特定的条件是体内肿瘤浸润的特征。因此，我们的研究表明，旨在揭示肿瘤浸润潜在分子机制的体外系统应该通过考虑结构异质性和化学梯度对细胞迁移的综合影响来考虑微环境的复杂性。
