The radial growth phase of malignant melanoma: multi-phase modelling, numerical simulations and linear stability analysis
The radial growth phase of malignant melanoma: multi-phase modelling, numerical simulations and linear stability analysis
复制标题
DOI：
10.1098/rsif.2010.0285
复制
发表时间：
2011-03-06
影响因子：
3.9
通讯作者：
Ben Amar, M.
中科院分区：
文献类型：
--
作者：
Ciarletta, P.;Foret, L.;Ben Amar, M.
尽管皮肤黑色素瘤的发病率相对较低，而且有可能在早期治愈，但它的致命性却不成比例。这项研究的目的是促进对黑色素瘤演变过程中微结构在病变皮肤形态变化发生中的作用的理解。作者对其径向生长阶段进行了生物力学分析，探讨了细胞间/基质连接在表皮侵袭初期的作用。原发黑色素瘤的径向生长阶段是在混合体的多阶段理论中模拟的，再现了皮肤层和表皮-真皮交界处的机械行为。理论分析考虑了那些已经被实验观察到的破坏正常表皮动态平衡的细胞过程。数值模拟表明，黑色素瘤细胞与基底板的粘附性丧失是促进肿瘤发生的基本生物力学特征。粘附性连接的松弛机制导致黑色素瘤细胞与基底层的粘附性丧失，以及由于E-钙粘附素的下调导致黑色素瘤细胞与邻近角质结细胞的粘附性丧失。最后，作者提供了黑色素瘤侵袭早期阶段肿瘤前沿长波不稳定性的数学证据。这些结果开启了将生长中的黑色素瘤的早期形态与其微环境的生物力学特征相关联的前景。
Cutaneous melanoma is disproportionately lethal despite its relatively low incidence and its potential for cure in the early stages. The aim of this study is to foster understanding of the role of microstructure on the occurrence of morphological changes in diseased skin during melanoma evolution. The authors propose a biomechanical analysis of its radial growth phase, investigating the role of intercellular/stromal connections on the initial stages of epidermis invasion. The radial growth phase of a primary melanoma is modelled within the multi-phase theory of mixtures, reproducing the mechanical behaviour of the skin layers and of the epidermal-dermal junction. The theoretical analysis takes into account those cellular processes that have been experimentally observed to disrupt homeostasis in normal epidermis. Numerical simulations demonstrate that the loss of adhesiveness of the melanoma cells both to the basal laminae, caused by deregulation mechanisms of adherent junctions, and to adjacent keratynocytes, consequent to a downregulation of E-cadherin, are the fundamental biomechanical features for promoting tumour initiation. Finally, the authors provide the mathematical proof of a long wavelength instability of the tumour front during the early stages of melanoma invasion. These results open the perspective to correlate the early morphology of a growing melanoma with the biomechanical characteristics of its micro-environment.