Control of epitheliomesenchymal transformation. II. Cross-modulation of cell adhesion and cytoskeletal systems in embryonic neural cells.
Control of epitheliomesenchymal transformation. II. Cross-modulation of cell adhesion and cytoskeletal systems in embryonic neural cells.
复制标题
控制上皮间充质转化。
DOI：
10.1006/dbio.1996.0135
复制
发表时间：
1996
影响因子：
2.7
通讯作者：
J. Minichiello
中科院分区：
文献类型：
--
作者：
Donald F. Newgreen;J. Minichiello
蛋白激酶(PK)抑制剂如星形孢子素诱导细胞外基质(ECM)分子纤维连接蛋白(Newgreen and Minichiello，Dev.比奥尔。170、91-101；1995)。我们在这里表明，这也发生在层粘连蛋白、玻璃连结蛋白、I型和IV型胶原上，但不存在于多聚赖氨酸或BSA上。在没有细胞-ECM黏附的情况下，星状孢子素能迅速增加而不是减少分离的神经原的凝聚力，并增加分离的神经细胞的聚集率。在没有细胞-细胞粘连的情况下(即与分离的细胞)，几乎所有的神经细胞在体外都能迅速粘连到纤维连接蛋白上，而星形孢子素对此只有很小的影响。在对照条件下，几乎没有神经细胞在纤维连接蛋白上扩散，但星形孢子素刺激了几乎所有细胞的扩散。当存在细胞-细胞粘连时，在星形孢子素存在的情况下，通过控制剪切从纤维连接蛋白底物上移出神经植块比在对照条件下更困难，但在实验和对照中，移位都是由于细胞-纤维连接蛋白粘连部位近端的细胞体断裂造成的。在培养的神经细胞中，无论是自发的还是由星状孢子素诱导的EMT，都涉及到环状F-肌动蛋白纤维的迅速减少和泛细胞质G-肌动蛋白的增加，如荧光素和DNase I标记所示。在自发性和诱导性EMT中，细胞-细胞连接处N-钙粘附素的免疫反应也发生了丢失。然而，在自发的EMT中，钙粘附素的变化先于肌动蛋白的变化，而在诱导性EMT中，则相反。结果提示，受PK抑制剂影响的参与EMT的分子为细胞骨架和连接元件。这些结果还表明，细胞-细胞间黏附分子、细胞-ECM黏附分子和细胞骨架分子之间的平衡交叉调制可以触发和协调EMT，而不需要直接的遗传监督。
Protein kinase (PK) inhibitors like staurosporine induce precocious epitheliomesenchymal transformation (EMT) of quail embryo neural anlagen cultured on the extracellular matrix (ECM) molecule fibronectin (Newgreen and Minichiello, Dev. Biol. 170, 91-101; 1995). We show here that this also occurs on laminin, vitronectin, and collagen type I and type IV, but not on polylysine or BSA. In the absence of cell-ECM adhesion, staurosporine produced a rapid increase in, rather than a loss of, cohesion in isolated neural anlagen and increased the rate of reaggregation of dissociated neural cells. In the absence of cell-cell adhesions (i.e., with dissociated cells), almost all neural cells rapidly adhered to fibronectin in vitro and staurosporine made only a marginal difference to this. Almost no neural cells spread on fibronectin in control conditions but staurosporine stimulated spreading by almost all cells. When cell-cell adhesions were present, neural anlage explants were more difficult to dislodge by controlled shear from fibronectin substrates in the presence of staurosporine than under control conditions, but in both experiments and controls dislodgment was due to the cell bodies breaking proximal to the cell-fibronectin adhesion sites. EMT in neural cells in culture, both spontaneous and induced by staurosporine, involved rapid reduction in circumferential F-actin fibers and an increase in pancytoplasmic G-actin, as shown by fluorescent phalloidin and DNase I labeling. Loss of immunoreactivity for N-cadherin at cell-cell junctions also occurred in both spontaneous and induced EMT. However, in spontaneous EMT the cadherin changes preceded the actin changes, whereas in induced EMT, the reverse occurred. The results suggest that the molecules involved in EMT which are affected by PK inhibitors are cytoskeletal and link elements. These results also suggest that balanced cross-modulation among cell-cell adhesion molecules, cell-ECM adhesion molecules, and cytoskeletal molecules can trigger and orchestrate EMT, without direct genetic supervision.