FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pancreatic adenocarcinoma cell lines.
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.
El-Hariry
I
I
Imperial Cancer Research Fund Molecular Oncology Unit, Imperial College School of Medicine, London, UK.
Pignatelli
M
M
Lemoine
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NR
D000230:Adenocarcinoma / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1