Neil S M, Eves P, Richardson B, Molife R, Lorigan P, Wagner M, Layton C, Morandini R, Ghanem G
University Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Sheffield, UK.
Pigment Cell Res. 2000;13 Suppl 8:68-72. doi: 10.1034/j.1600-0749.13.s8.13.x.
The invasion of melanoma is complex and multi-staged and involves changes in both cell/extracellular matrix (ECM) and cell/cell interactions. Female steroids and alpha-MSH have also been reported to influence metastatic melanoma progression, but their mechanisms of action are unknown. Accordingly, our aim was to establish in vitro models to examine (a) the influence of sex steroids and alpha-melanocyte-stimulating hormone (alpha-MSH) on tumour invasion and the influence of (b) ECM proteins and (c) adjacent cells on melanoma invasion. In the first model, melanoma cell invasion through fibronectin over 20 hr under serum-free conditions was used to investigate the effects of 17beta-oestradiol and oestrone on the invasion of human melanoma cell lines, A375-SM and HBL. A375-SM, but not HBL cells, proved very susceptible to inhibition by female steroids. However, invasion of the HBL line was inhibited by alpha-MSH. Using the second model of reconstructed human skin based on de-epidermised acellular dermis, we found that the HBL cells on their own failed to invade into the dermis (irrespective of the presence or absence of the basement membrane). However, there was a significant synergistic interaction between keratinocytes, fibroblasts and HBL cells, such that a modest invasion of HBLs into the dermis was seen within 2 weeks when other skin cells were present. In contrast, A375-SM cells showed a significant ability to invade the dermis in the absence of other cells, with less invasion when other skin cells were present. In summary, these models have provided new information on the extent to which melanoma cell invasion is sensitive to oestrogenic steroids and to alpha-MSH and to interaction, not only with adjacent skin cells but also to the presence of basement membrane antigens.
黑色素瘤的侵袭过程复杂且具有多阶段性，涉及细胞/细胞外基质（ECM）以及细胞/细胞间相互作用的改变。据报道，女性甾体激素和α-促黑素（α-MSH）也会影响转移性黑色素瘤的进展，但其作用机制尚不清楚。因此，我们的目标是建立体外模型来研究：（a）性甾体激素和α-黑素细胞刺激素（α-MSH）对肿瘤侵袭的影响，以及（b）ECM蛋白和（c）相邻细胞对黑色素瘤侵袭的影响。在第一个模型中，在无血清条件下，利用黑色素瘤细胞在20小时内穿过纤连蛋白的侵袭情况，研究17β-雌二醇和雌酮对人黑色素瘤细胞系A375-SM和HBL侵袭的影响。结果显示，A375-SM细胞对女性甾体激素的抑制作用非常敏感，而HBL细胞则不然。然而，α-MSH可抑制HBL细胞系的侵袭。在基于去表皮无细胞真皮构建的人重组皮肤的第二个模型中，我们发现单独的HBL细胞无法侵入真皮（无论是否存在基底膜）。然而，角质形成细胞、成纤维细胞和HBL细胞之间存在显著的协同相互作用，因此当存在其他皮肤细胞时，在2周内可见HBL细胞适度侵入真皮。相反，A375-SM细胞在没有其他细胞的情况下具有显著的侵入真皮的能力，而当存在其他皮肤细胞时，其侵袭能力则较弱。总之，这些模型提供了新的信息，表明黑色素瘤细胞侵袭对雌激素甾体激素、α-MSH以及不仅与相邻皮肤细胞相互作用，还与基底膜抗原的存在敏感的程度。
