Eves P, Layton C, Hedley S, Dawson R A, Wagner M, Morandini R, Ghanem G, Mac Neil S
Division of Clinical Sciences, Clinical Sciences Centre, Northern General Hospital, Sheffield, UK.
Br J Dermatol. 2000 Feb;142(2):210-22. doi: 10.1046/j.1365-2133.2000.03287.x.
The purpose of this study was to compare the invasive properties of normal human cutaneous melanocytes and of a cutaneous melanoma cell line (HBL) in a three-dimensional model of reconstructed human skin. Specifically, we asked to what extent the pigmentary and invasive behaviour of both cells is influenced by their interaction with adjacent skin cells (keratinocytes and fibroblasts) and the basement membrane (BM). In the presence of a BM, normal human melanocytes within this model remained within the basal layer of keratinocytes and did not pigment spontaneously. When the BM was removed, melanocytes were found suprabasally and pigmented extensively. No significant invasion of melanocytes into the dermis was detected in the presence or absence of the BM. HBL melanoma cells showed no significant ability to invade into the dermis in the absence of other cells, irrespective of the presence or absence of the BM. However, when added to keratinocytes and fibroblasts, HBL cells showed a capacity to invade into the dermis, both in the presence and absence of the BM. Associated with HBL invasion into the dermis, we noted significant keratinocyte entry into the dermis. On their own, keratinocytes entered the dermis in the absence of the BM but showed no significant penetration into the dermis when the BM was present. In summary, this model demonstrates clear differences between melanocytes and a melanoma cell line with respect to their invasive properties. It also allows demonstration of interactions between cells, and between cells and the BM. The study also provides evidence for a synergistic interaction between this melanoma cell line and keratinocytes in penetrating the BM.
本研究的目的是在重建人皮肤的三维模型中比较正常人皮肤黑素细胞和一种皮肤黑色素瘤细胞系（HBL）的侵袭特性。具体而言，我们探究了这两种细胞的色素沉着和侵袭行为在多大程度上受其与相邻皮肤细胞（角质形成细胞和成纤维细胞）及基底膜（BM）相互作用的影响。在存在基底膜的情况下，该模型中的正常人黑素细胞保留在角质形成细胞的基底层内，且不会自发色素沉着。去除基底膜后，黑素细胞出现在基底上层并大量色素沉着。无论有无基底膜，均未检测到黑素细胞有明显侵入真皮的情况。在没有其他细胞的情况下，无论有无基底膜，HBL黑色素瘤细胞均未表现出明显的侵入真皮的能力。然而，当添加到角质形成细胞和成纤维细胞中时，无论有无基底膜，HBL细胞均表现出侵入真皮的能力。与HBL侵入真皮相关的是，我们注意到角质形成细胞也大量进入真皮。单独来看，角质形成细胞在没有基底膜时会进入真皮，但在有基底膜时则未表现出明显的向真皮内的穿透。总之，该模型显示了黑素细胞和黑色素瘤细胞系在侵袭特性方面的明显差异。它还能够展示细胞之间以及细胞与基底膜之间的相互作用。该研究还为这种黑色素瘤细胞系与角质形成细胞在穿透基底膜方面的协同相互作用提供了证据。
