Sroka J, von Gunten M, Dunn G A, Keller H U
Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland.
Int J Biochem Cell Biol. 2002 Jul;34(7):882-99. doi: 10.1016/s1357-2725(01)00178-9.
We characterised two sublines of Walker carcinosarcoma cells generated by epigenetic changes. Subline 1 cells were mostly polarised and made no or only non-adhesive cell-substratum contacts. Subline 2 cells were spread, adhesive and mainly non-polar. Subline 1 cells migrate in a non-adhesive mode which is very efficient but operates only in a 3D environment, whereas subline 2 cells migrate in an adhesive mode, which is less efficient but works on 2D and 3D substrata. Nocodazole had little or no effect on shape, polarity and locomotion of subline 1 cells. In glass-adherent subline 2 cells, 10(-6)M nocodazole increased the proportion of polarised cells migrating in an adhesive mode and decreased adhesion to the substratum, whereas 10(-5)M nocodazole further reduced the contacts and the cells reverted to a non-adhesive mode of locomotion. When non-polar subline 2 cells were detached mechanically or by nocodazole, they became polarised and morphologically indistinguishable from non-adherent subline 1 cells. On more adhesive plastic substrata, subline 2 cells produced heterogeneous responses to nocodazole including loss of polarity. The phenotypes of Walker carcinosarcoma sublines have similarities with a broad range of cell types ranging from leucocytes to fibroblast-like cells, suggesting that these phenotypic differences can be controlled by the adhesive and contractile state rather than the cell type. Adhesion modulates contractility (isometric or isotonic contraction) and vice versa and this determines morphology (shape, F-actin, myosin and alpha-actinin), locomotion and responses to microtubule-disassembly. The model may be applied to analyse the mechanisms controlling the phenotype of cells in general.
我们对通过表观遗传变化产生的沃克癌肉瘤细胞的两个亚系进行了表征。亚系1细胞大多呈极化状态，与细胞基质无接触或仅有非粘附性接触。亚系2细胞呈铺展状、具有粘附性且主要为非极化状态。亚系1细胞以非粘附模式迁移，这种模式非常高效，但仅在三维环境中起作用，而亚系2细胞以粘附模式迁移，效率较低，但在二维和三维基质上均可发挥作用。诺考达唑对亚系1细胞的形态、极性和运动几乎没有影响。在玻璃粘附的亚系2细胞中，10⁻⁶M的诺考达唑增加了以粘附模式迁移的极化细胞的比例，并降低了对基质的粘附性，而10⁻⁵M的诺考达唑进一步减少了细胞接触，细胞恢复为非粘附性运动模式。当非极化的亚系2细胞通过机械方法或诺考达唑脱离时，它们会极化，在形态上与非粘附性的亚系1细胞无法区分。在更具粘附性的塑料基质上，亚系2细胞对诺考达唑产生了异质性反应，包括极性丧失。沃克癌肉瘤亚系的表型与从白细胞到成纤维细胞样细胞等广泛的细胞类型具有相似性，这表明这些表型差异可能由粘附和收缩状态而非细胞类型控制。粘附调节收缩性（等长或等张收缩），反之亦然，这决定了形态（形状、F-肌动蛋白、肌球蛋白和α-辅肌动蛋白）、运动以及对微管解聚的反应。该模型可用于总体分析控制细胞表型的机制。
