title: 1α,25(OH)₂D₃ inhibits FGF-2 release from oral squamous cell carcinoma cells through down-regulation of HBp17/FGFBP-1.
abstract: 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.
authors.affiliation: 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.
authors.forename: S N Zawani B
authors.initials: SN
authors.lastname: Rosli
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Shintani
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Toratani
authors.forename: Emiko
authors.initials: E
authors.lastname: Usui
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D018167:Receptors, Calcitriol
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D006887:Hydroxycholecalciferols; D036341:Intercellular Signaling Peptides and Proteins; D018167:Receptors, Calcitriol; D016222:Fibroblast Growth Factor 2; C070699:FGFBP1 protein, human