Dewhurst L O, Rennie I G, MacNeil S
University of Sheffield Department of Medicine, Clinical Sciences Centre, Northern General Hospital, UK.
Melanoma Res. 1998 Aug;8(4):303-11. doi: 10.1097/00008390-199808000-00003.
The literature concerning cytoskeletal changes and metastatic progression is unresolved, some studies suggesting a positive association between the ability of cells to organize their cytoskeleton and others suggesting an inverse correlation. In an attempt to learn more about cytoskeletal changes and the ability of melanoma cells to interact with extracellular matrix proteins we examined the effects of pharmacological manipulation of cell attachment and cell invasion through fibronectin on levels of F-actin and vimentin in a highly metastatic cutaneous melanoma cell line (A375-SM cells). Additionally, we examined whether any correlation existed between the levels of the cytoskeletal proteins and subpopulations of the cell line of varying invasive ability. We report that agents which reduced cell attachment to plastic and invasion through fibronectin in vitro (tamoxifen, N-desmethyltamoxifen and 17beta-oestradiol) caused increases in levels of F-actin and vimentin, whereas agents which did not affect attachment or invasion (4-hydroxytamoxifen and dihydrotestosterone) had little or no effect on the cytoskeletal proteins. In contrast, however, those cells which were most effective at invading through fibronectin were significantly better at acutely increasing their levels of F-actin and vimentin than less invasive cells. We speculate that the ability to rapidly and possibly reversibly alter the cytoskeleton might be associated with metastatically successful cells in vivo.
关于细胞骨架变化与转移进展的文献尚无定论,一些研究表明细胞组织其细胞骨架的能力之间存在正相关,而另一些研究则表明存在负相关。为了更多地了解细胞骨架变化以及黑色素瘤细胞与细胞外基质蛋白相互作用的能力,我们研究了通过药物处理细胞附着以及细胞通过纤连蛋白侵袭对一种高转移性皮肤黑色素瘤细胞系(A375-SM细胞)中F-肌动蛋白和波形蛋白水平的影响。此外,我们还研究了细胞骨架蛋白水平与具有不同侵袭能力的细胞系亚群之间是否存在任何相关性。我们报告称,在体外降低细胞与塑料的附着以及通过纤连蛋白侵袭的药物(他莫昔芬、N-去甲基他莫昔芬和17β-雌二醇)会导致F-肌动蛋白和波形蛋白水平升高,而不影响附着或侵袭的药物(4-羟基他莫昔芬和二氢睾酮)对细胞骨架蛋白几乎没有影响。然而,相比之下,那些最能有效通过纤连蛋白侵袭的细胞在急性增加其F-肌动蛋白和波形蛋白水平方面明显优于侵袭性较弱的细胞。我们推测,快速且可能可逆地改变细胞骨架的能力可能与体内转移成功的细胞有关。