Marzioni D, Lorenzi T, Mazzucchelli R, Capparuccia L, Morroni M, Fiorini R, Bracalenti C, Catalano A, David G, Castellucci M, Muzzonigro G, Montironi R
Department of Molecular Pathology and Innovative Therapies, Marche Polytechnic University, School of Medicine, Ancona, Italy.
Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):627-38. doi: 10.1177/039463200902200308.
Basic fibroblast growth factor (bFGF) is a heparin-binding cationic protein involved in a variety of pathological conditions including angiogenesis and solid tumour growth. The basic fibroblast growth factor receptor (FGFR) family comprises at least 4 high affinity tyrosine kinase receptors that require syndecans for their function. Mounting evidence indicates that syndecans, that bind both bFGF and their FGFRs, will act as stimulators, whereas syndecans that only bind bFGF will act as inhibitors of signaling by sequestering the growth factor. Recent findings have highlighted the importance of syndecans in urological cancers. The aim of this study is to investigate the expression of bFGF, its receptors (R1 and R2) and syndecans (1-4) in invasive urothelial carcinoma and normal-looking urothelium by Western blotting, RT-PCR, and immunohistochemistry analyses. Interestingly, bFGF, FGFR1 and FGFR2 protein levels statistically increased in bladder cancer tissues. mRNA of FGFR1 and syndecans (1-4), showed a statistically significant increase while an mRNA increase in the other molecules analysed was not significant. bFGF, its receptors and syndecan immunostaining were mainly present in the urothelium both in normal-looking tissues and urothelial neoplastic cells. In conclusion, our data report that the bFGF, FGFR and syndecan expressions are altered in bladder tumours.
碱性成纤维细胞生长因子（bFGF）是一种肝素结合阳离子蛋白，参与包括血管生成和实体瘤生长在内的多种病理过程。碱性成纤维细胞生长因子受体（FGFR）家族至少由4种高亲和力酪氨酸激酶受体组成，其功能需要多配体聚糖。越来越多的证据表明，既能结合bFGF又能结合其FGFR的多配体聚糖将起到刺激作用，而仅结合bFGF的多配体聚糖将通过隔离生长因子起到信号传导抑制剂的作用。最近的研究结果突出了多配体聚糖在泌尿系统癌症中的重要性。本研究的目的是通过蛋白质印迹法、逆转录-聚合酶链反应（RT-PCR）和免疫组织化学分析，研究bFGF及其受体（R1和R2）和多配体聚糖（1-4）在浸润性尿路上皮癌和外观正常的尿路上皮中的表达。有趣的是，膀胱癌组织中bFGF、FGFR1和FGFR2的蛋白水平在统计学上有所增加。FGFR1和多配体聚糖（1-4）的mRNA显示出统计学上的显著增加，而所分析的其他分子的mRNA增加不显著。bFGF及其受体和多配体聚糖免疫染色主要存在于外观正常组织和尿路上皮肿瘤细胞的尿路上皮中。总之，我们的数据表明，bFGF、FGFR和多配体聚糖的表达在膀胱肿瘤中发生了改变。
