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1α,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells through down-regulation of HBp17/FGFBP-1

  • S. N. Zawani B. Rosli
  • Tomoaki Shintani
  • Shigeaki Toratani
  • Emiko Usui
  • Tetsuji OkamotoEmail author
Report

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.

Keywords

Oral squamous cell carcinoma HBp17/FGFBP-1 FGF-2 1α,25(OH)2D3 Vitamin D receptor 

Notes

Acknowledgments

This research was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology to T.O. (grant number 24390456) and T. S. (25463109). The authors thank Dr. J. Denry Sato for editorial assistance.

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Copyright information

© The Society for In Vitro Biology 2014

Authors and Affiliations

  • S. N. Zawani B. Rosli
    • 1
  • Tomoaki Shintani
    • 2
  • Shigeaki Toratani
    • 3
  • Emiko Usui
    • 3
  • Tetsuji Okamoto
    • 4
    Email author
  1. 1.Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Center of Oral Clinical ExaminationHiroshima University HospitalHiroshimaJapan
  3. 3.Oral Maxillofacial SurgeryHiroshima University HospitalHiroshimaJapan
  4. 4.Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Applied Life Sciences, Institute of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan

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