Laboratoire de Physique Statistique de l'École Normale Supérieure, 24 rue Lhomond, F75231 Paris Cedex 05, France.
J R Soc Interface. 2011 Mar 6;8(56):345-68. doi: 10.1098/rsif.2010.0285. Epub 2010 Jul 23.
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.
尽管黑色素瘤发病率相对较低，且在早期阶段有治愈的可能，但它的死亡率却不成比例。本研究旨在深入了解微观结构在黑色素瘤演变过程中对病变皮肤形态变化发生的作用。作者提出了对其放射状生长阶段的生物力学分析，研究了细胞间/基质连接在表皮入侵初始阶段的作用。在多相混合物理论中对原发性黑色素瘤的放射状生长阶段进行建模，重现皮肤各层和表皮-真皮连接的力学行为。理论分析考虑了那些已通过实验观察到的扰乱正常表皮内稳态的细胞过程。数值模拟表明，黑色素瘤细胞与基底膜的黏附性丧失（由黏着连接的调节机制引起），以及与相邻角质形成细胞的黏附性丧失（由于 E-钙黏蛋白的下调），是促进肿瘤发生的基本生物力学特征。最后，作者提供了肿瘤前沿在黑色素瘤入侵早期阶段出现长波长不稳定性的数学证明。这些结果为将不断生长的黑色素瘤的早期形态与其微环境的生物力学特征联系起来开辟了前景。
