Turner Stephen, Sherratt Jonathan A
Centre for Theoretical Modelling in Medicine, Heriot-Watt University, Edinburgh EH14 4AS, UK.
J Theor Biol. 2002 May 7;216(1):85-100. doi: 10.1006/jtbi.2001.2522.
We develop a discrete model of malignant invasion using a thermodynamic argument. An extension of the Potts model is used to simulate a population of malignant cells experiencing interactions due to both homotypic and heterotypic adhesion while also secreting proteolytic enzymes and experiencing a haptotactic gradient. In this way we investigate the influence of changes in cell-cell adhesion on the invasion process. We demonstrate that the morphology of the invading front is influenced by changes in the adhesiveness parameters, and detail how the invasiveness of the tumour is related to adhesion. We show that cell-cell adhesion has less of an influence on invasion compared with cell-medium adhesion, and that increases in both proteolytic enzyme secretion rate and the coefficient of haptotaxis act in synergy to promote invasion. We extend the simulation by including proliferation, and, following experimental evidence, develop an algorithm for cell division in which the mitotic rate is explicitly related to changes in the relative magnitudes of homotypic and heterotypic adhesiveness. We show that although an increased proliferation rate usually results in an increased depth of invasion into the extracellular matrix, it does not invariably do so, and may, indeed, cause invasiveness to be reduced.
我们利用热力学观点建立了一个恶性侵袭的离散模型。Potts模型的扩展被用于模拟一群恶性细胞，这些细胞由于同型和异型黏附而相互作用，同时还分泌蛋白水解酶并经历趋触性梯度。通过这种方式，我们研究了细胞间黏附变化对侵袭过程的影响。我们证明侵袭前沿的形态受黏附参数变化的影响，并详细阐述了肿瘤的侵袭性与黏附的关系。我们表明，与细胞-基质黏附相比，细胞间黏附对侵袭的影响较小，并且蛋白水解酶分泌率和趋触性系数的增加协同作用以促进侵袭。我们通过纳入增殖来扩展模拟，并根据实验证据开发了一种细胞分裂算法，其中有丝分裂率与同型和异型黏附相对大小的变化明确相关。我们表明，尽管增殖率增加通常会导致向细胞外基质侵袭的深度增加，但并非总是如此，实际上可能会导致侵袭性降低。
