Lin Shao-Zhen, Li Bo, Xu Guang-Kui, Feng Xi-Qiao
Institute of Biomechanics and Medical Engineering, AML, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.
Institute of Biomechanics and Medical Engineering, AML, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.
J Biomech. 2017 Feb 8;52:140-147. doi: 10.1016/j.jbiomech.2016.12.035. Epub 2016 Dec 29.
Tumorigenesis often involves specific changes in cell motility and intercellular adhesion. Understanding the collective cancer cell behavior associated with these specific changes could facilitate the detection of malignant characteristics during tumor growth and invasion. In this study, a cellular vertex model is developed to investigate the collective dynamics of a disk-like aggregate of cancer cells confined in a confluent monolayer of normal cells. The effects of intercellular adhesion and cell motility on tumor progression are examined. It is found that the stresses in both the cancer cells and the normal cells increase with tumor growth, resulting in a crowded environment and enhanced cell apoptosis. The intercellular adhesion between cancer cells and normal cells is revealed to promote tumor growth and invasion. The tumor invasion dynamics hinges on the motility of cancer cells. The cancer cells could orchestrate into different collective migration modes, e.g., directional migration and rotational oscillations, dictated by the competition between cell persistence and local coordination. Phase diagrams are established to reveal the competitive mechanisms. This work highlights the role of mechanics in regulating tumor growth and invasion.
肿瘤发生通常涉及细胞运动性和细胞间黏附的特定变化。了解与这些特定变化相关的癌细胞集体行为，有助于在肿瘤生长和侵袭过程中检测恶性特征。在本研究中，开发了一种细胞顶点模型，以研究局限于正常细胞汇合单层中的盘状癌细胞聚集体的集体动力学。研究了细胞间黏附力和细胞运动性对肿瘤进展的影响。研究发现，随着肿瘤生长，癌细胞和正常细胞中的应力都会增加，导致环境拥挤和细胞凋亡增加。结果表明，癌细胞与正常细胞之间的细胞间黏附促进了肿瘤的生长和侵袭。肿瘤侵袭动力学取决于癌细胞的运动性。癌细胞可以通过细胞持续性和局部协调性之间的竞争，编排成不同的集体迁移模式，如定向迁移和旋转振荡。建立相图以揭示竞争机制。这项工作突出了力学在调节肿瘤生长和侵袭中的作用。
