Watabe M, Matsumoto K, Nakamura T, Takeichi M
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Cell Struct Funct. 1993 Apr;18(2):117-24. doi: 10.1247/csf.18.117.
Hepatocyte growth factor (HGF) is known to induce the dispersion of epithelial cells, as scatter factor. On the other hand, cadherins play a crucial role in connecting cells together. Two groups of cadherins are involved in epithelial cell adhesion, those locating in adherens junctions (AJ) and in desmosomes. Here, we examined the effect of HGF on the function of these cadherins in keratinocyte cell lines F and 308R, which expressed E- and P-cadherin in AJ (referred to as AJ cadherins) and desmoplakin in desmosomes. In the presence of HGF, these cells spread more extensively than in control cultures and their associations apparently loosened. However, they maintained cell-cell contacts where cadherins and desmoplakin concentrated, although the level of the concentration was reduced by HGF treatment. When antibodies to E- and P-cadherins were added to cultures of these cells without HGF, AJ cadherins were redistributed into non-junctional areas of the cells, but desmoplakin still localized at cell-cell boundaries. When HGF was added together with anti-AJ cadherin antibodies to the cultures, cell-cell contacts were now disrupted. In these cultures, not only AJ cadherins but also desmoplakin were lost at cell-cell contact sites, indicating that HGF can disrupt desmosomal cell-cell adhesion when AJ cadherins are inactive. These results suggest that, although HGF cannot block cadherin-mediated cell-cell adhesion when the entire cadherin system is intact, it might modulate the activities of cadherins, especially, of desmosomal cadherins.
已知肝细胞生长因子（HGF）作为散射因子可诱导上皮细胞分散。另一方面，钙黏蛋白在将细胞连接在一起方面起着关键作用。两组钙黏蛋白参与上皮细胞黏附，一组位于黏着连接（AJ），另一组位于桥粒。在此，我们研究了HGF对角质形成细胞系F和308R中这些钙黏蛋白功能的影响，这两种细胞系在AJ中表达E-钙黏蛋白和P-钙黏蛋白（称为AJ钙黏蛋白），在桥粒中表达桥粒斑蛋白。在HGF存在的情况下，这些细胞比在对照培养物中更广泛地铺展，并且它们之间的连接明显松弛。然而，它们在钙黏蛋白和桥粒斑蛋白聚集的地方维持着细胞间接触，尽管通过HGF处理后聚集水平降低。当在没有HGF的情况下将抗E-钙黏蛋白和抗P-钙黏蛋白抗体添加到这些细胞的培养物中时，AJ钙黏蛋白重新分布到细胞的非连接区域，但桥粒斑蛋白仍定位在细胞间边界。当将HGF与抗AJ钙黏蛋白抗体一起添加到培养物中时，细胞间接触现在被破坏。在这些培养物中，不仅AJ钙黏蛋白，而且桥粒斑蛋白在细胞间接触位点也消失了，这表明当AJ钙黏蛋白失活时，HGF可以破坏桥粒介导的细胞间黏附。这些结果表明，尽管当整个钙黏蛋白系统完整时HGF不能阻断钙黏蛋白介导的细胞间黏附，但它可能调节钙黏蛋白的活性，尤其是桥粒钙黏蛋白的活性。
