1α,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells through down-regulation of HBp17/FGFBP-1
1α,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells through down-regulation of HBp17/FGFBP-1
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DOI：
10.1007/s11626-014-9787-5
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发表时间：
2014-06
期刊：
影响因子：
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通讯作者：
S. Rosli;T. Shintani;S. Toratani;E. Usui;T. Okamoto
中科院分区：
文献类型：
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作者：
S. Rosli;T. Shintani;S. Toratani;E. Usui;T. Okamoto
肝素结合蛋白 17/成纤维细胞生长因子结合蛋白-1 (HBp17/FGFBP-1，GenBank 登录号 NP-005121) 以其作为成纤维细胞生长因子-2 (FGF-2) 伴侣的作用而闻名，FGF-2 在血管生成和促进肿瘤生长中发挥着至关重要的作用。 HBp17/FGFBP-1 已被提议作为许多癌症的候选生物标志物，因为它经常被发现在许多癌症类型中升高，包括口腔鳞状细胞癌 (OSCC) 的组织和细胞系。此前，我们报道了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 1α,25(OH)2D3 处理 OSCC 细胞可抑制细胞核和细胞质中的 HBp17/FGFBP-1 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的治疗潜力。
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)2D3suppressed 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)2D3on 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)2D3suppressed 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)2D3to 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.