Jiang Chongming, Cui Chunyan, Zhong Weirong, Li Gang, Li Li, Shao Yuanzhi
School of Physics, Sun Yat-sen University, Guangzhou, 510275, China.
BGI-Research in Shenzhen, Shenzhen, 518083, China.
J Biol Phys. 2016 Oct;42(4):637-658. doi: 10.1007/s10867-016-9427-2. Epub 2016 Sep 27.
We study in silico the influence of host tissue inhomogeneity on tumor cell proliferation and diffusion by simulating the mobility of a tumor on percolation clusters with different homogeneities of surrounding tissues. The proliferation and diffusion of a tumor in an inhomogeneous tissue could be characterized in the framework of the percolation theory, which displays similar thresholds (0.54, 0.44, and 0.37, respectively) for tumor proliferation and diffusion in three kinds of lattices with 4, 6, and 8 connecting near neighbors. Our study reveals the existence of a critical transition concerning the survival and diffusion of tumor cells with leaping metastatic diffusion movement in the host tissues. Tumor cells usually flow in the direction of greater pressure variation during their diffusing and infiltrating to a further location in the host tissue. Some specific sites suitable for tumor invasion were observed on the percolation cluster and around these specific sites a tumor can develop into scattered tumors linked by some advantage tunnels that facilitate tumor invasion. We also investigate the manner that tissue inhomogeneity surrounding a tumor may influence the velocity of tumor diffusion and invasion. Our simulation suggested that invasion of a tumor is controlled by the homogeneity of the tumor microenvironment, which is basically consistent with the experimental report by Riching et al. as well as our clinical observation of medical imaging. Both simulation and clinical observation proved that tumor diffusion and invasion into the surrounding host tissue is positively correlated with the homogeneity of the tissue.
我们通过模拟肿瘤在具有不同周围组织均匀性的渗流簇上的移动性,对宿主组织不均匀性对肿瘤细胞增殖和扩散的影响进行了计算机模拟研究。肿瘤在不均匀组织中的增殖和扩散可以在渗流理论的框架内进行表征,该理论在具有4、6和8个近邻连接的三种晶格中,肿瘤增殖和扩散分别显示出相似的阈值(分别为0.54、0.44和0.37)。我们的研究揭示了在宿主组织中具有跳跃式转移扩散运动的肿瘤细胞的存活和扩散存在临界转变。肿瘤细胞在向宿主组织中更远的位置扩散和浸润时,通常会朝着压力变化更大的方向流动。在渗流簇上观察到了一些适合肿瘤侵袭的特定部位,在这些特定部位周围,肿瘤可以发展成由一些有利于肿瘤侵袭的优势通道相连的散在肿瘤。我们还研究了肿瘤周围组织不均匀性可能影响肿瘤扩散和侵袭速度的方式。我们的模拟表明,肿瘤的侵袭受肿瘤微环境均匀性的控制,这与Riching等人的实验报告以及我们对医学影像的临床观察基本一致。模拟和临床观察均证明,肿瘤向周围宿主组织的扩散和侵袭与组织的均匀性呈正相关。