Rosli S N Zawani B, Shintani Tomoaki, Toratani Shigeaki, Usui Emiko, Okamoto Tetsuji
Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
In Vitro Cell Dev Biol Anim. 2014 Oct;50(9):802-6. doi: 10.1007/s11626-014-9787-5. Epub 2014 Jun 18.
Heparin-binding protein 17/fibroblast growth factor binding protein-1 (HBp17/FGFBP-1, GenBank accession no. NP-005121) is prominent for its role as the chaperone for fibroblast growth factor-2 (FGF-2), which plays a crucial role in angiogenesis as well as promoting tumor growth. HBp17/FGFBP-1 has been proposed as a candidate biomarker for a number of cancers since it is frequently found to be elevated in many cancer types including in the tissue and cell lines of oral squamous cell carcinomas (OSCC). Previously, we reported that 1α,25(OH)2D3 suppressed the HBp17/FGFBP-1 expression in OSCC by inhibiting nuclear factor-kappaB (NF-κB) expression via vitamin D3 receptor (VDR). In this paper, to further characterize the inhibitory effect of 1α,25(OH)2D3 on HBp17/FGFBP-1, we examined the cellular localization of HBp17/FGFBP-1 protein and FGF-2 protein in the UE OSCC cell line. We found that the treatment of OSCC cells with 40-nM 1α,25(OH)2D3 suppressed HBp17/FGFBP-1 expression both in the nucleus and cytosol and reduced FGF-2 release into the culture medium. The expression of HBp17/FGFBP-1 and FGF-2 was analyzed by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). In summary, the ability of 1α,25(OH)2D3 to suppress the expression of HBp17/FGFBP-1 and FGF-2 strongly suggests a therapeutic potential as a molecular-targeted anticancer drug for FGF-dependent cancers.
肝素结合蛋白17/成纤维细胞生长因子结合蛋白-1（HBp17/FGFBP-1，基因库登录号：NP-005121）因其作为成纤维细胞生长因子-2（FGF-2）的伴侣蛋白而备受关注，FGF-2在血管生成以及促进肿瘤生长中起着关键作用。由于HBp17/FGFBP-1在包括口腔鳞状细胞癌（OSCC）组织和细胞系在内的多种癌症类型中经常被发现升高，因此它被提议作为多种癌症的候选生物标志物。此前，我们报道1α,25(OH)2D3通过维生素D3受体（VDR）抑制核因子-κB（NF-κB）表达，从而抑制OSCC中HBp17/FGFBP-1的表达。在本文中，为了进一步表征1α,25(OH)2D3对HBp17/FGFBP-1的抑制作用，我们检测了UE OSCC细胞系中HBp17/FGFBP-1蛋白和FGF-2蛋白的细胞定位。我们发现用40 nM的1α,25(OH)2D3处理OSCC细胞可抑制细胞核和细胞质中HBp17/FGFBP-1的表达，并减少FGF-2释放到培养基中。通过免疫荧光和酶联免疫吸附测定（ELISA）分析了HBp17/FGFBP-1和FGF-2的表达。总之，1α,25(OH)2D3抑制HBp17/FGFBP-1和FGF-2表达的能力强烈表明其作为FGF依赖性癌症的分子靶向抗癌药物具有治疗潜力。
