El-Hariry I, Pignatelli M, Lemoine N R
Imperial Cancer Research Fund Molecular Oncology Unit, Imperial College School of Medicine, London, UK.
Br J Cancer. 2001 Jun 15;84(12):1656-63. doi: 10.1054/bjoc.2001.1813.
Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) have been increasingly recognized to play an important role in the pathobiology of pancreatic malignancy. We have investigated the effects of FGF-1 and FGF-2 on the behaviour and adhesion properties of human pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF) that were previously characterised for the expression of FGFRs. Here we show that exposure to FGF-1 and FGF-2 leads to significant and dose-dependent increase in E-cadherin-dependent cell-cell adhesion, tubular differentiation, and a reduced capacity to invade collagen gels. FGF stimulation produces phosphorylation of E-cadherin and beta-catenin on tyrosine residues, as well as increased E-cadherin localisation to the cytoplasmic membrane and association with FGFR1 demonstrable by coimmunoprecipitation. These results demonstrate that FGF-1 and FGF-2 may be involved in the regulation of cell adhesion, differentiation and invasion of pancreatic cancer.
成纤维细胞生长因子(FGFs)和成纤维细胞生长因子受体(FGFRs)在胰腺恶性肿瘤的病理生物学中发挥重要作用,这一点已得到越来越多的认可。我们研究了FGF-1和FGF-2对人胰腺腺癌细胞系(BxPc3、T3M4和HPAF)行为和黏附特性的影响,这些细胞系之前已对FGFRs的表达进行了表征。在此我们表明,暴露于FGF-1和FGF-2会导致E-钙黏蛋白依赖性细胞间黏附、管状分化显著且呈剂量依赖性增加,以及侵袭胶原凝胶的能力降低。FGF刺激会使E-钙黏蛋白和β-连环蛋白的酪氨酸残基发生磷酸化,同时E-钙黏蛋白在细胞质膜上的定位增加,并通过免疫共沉淀证明其与FGFR1相关。这些结果表明,FGF-1和FGF-2可能参与了胰腺癌细胞黏附、分化和侵袭的调控。