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Journal of Neuro-Oncology

, Volume 118, Issue 1, pp 49–60 | Cite as

Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme

  • Débora G. Salomón
  • María E. Fermento
  • Norberto A. Gandini
  • María J. Ferronato
  • Julián Arévalo
  • Jorge Blasco
  • Nancy C. Andrés
  • Jean C. Zenklusen
  • Alejandro C. Curino
  • María M. Facchinetti
Laboratory Investigation

Abstract

Vitamin D and its analogs have been shown to display anti-proliferative effects in a wide variety of cancer types including glioblastoma multiforme (GBM). These anticancer effects are mediated by its active metabolite, 1α, 25-dihydroxyvitamin D3 (calcitriol) acting mainly through vitamin D receptor (VDR) signaling. In addition to its involvement in calcitriol action, VDR has also been demonstrated to be useful as a prognostic factor for some types of cancer. However, to our knowledge, there are no studies evaluating the expression of VDR protein and its association with outcome in gliomas. Therefore, we investigated VDR expression by using immunohistochemical analysis in human glioma tissue microarrays, and analyzed the association between VDR expression and clinico-pathological parameters. We further investigated the effects of genetic and pharmacologic modulation of VDR on survival and migration of glioma cell lines. Our data demonstrate that VDR is increased in tumor tissues when compared with VDR in non-malignant brains, and that VDR expression is associated with an improved outcome in patients with GBM. We also show that both genetic and pharmacologic modulation of VDR modulates GBM cellular migration and survival and that VDR is necessary for calcitriol-mediated effects on migration. Altogether these results provide some limited evidence supporting a role for VDR in glioma progression.

Keywords

Vitamin D receptor Human GBM Tissue microarray Biomarker Survival Prognosis 

Notes

Acknowledgments

This work was supported by grants from National Council of Scientific and Technical Research (CONICET), National Agency for the Promotion of Science and Technology (ANPCyT) and from the Technical Secretary of the Universidad Nacional del Sur. D. Salomón is a recipient of fellowship from Conicet.

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

11060_2014_1416_MOESM1_ESM.pdf (237 kb)
Supplementary material 1 (PDF 236 kb)
11060_2014_1416_MOESM2_ESM.pdf (423 kb)
Supplementary material 2 (PDF 422 kb)
11060_2014_1416_MOESM3_ESM.pdf (232 kb)
Supplementary material 3 (PDF 232 kb)
11060_2014_1416_MOESM4_ESM.pdf (253 kb)
Supplementary material 4 (PDF 253 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Débora G. Salomón
    • 1
  • María E. Fermento
    • 1
  • Norberto A. Gandini
    • 1
  • María J. Ferronato
    • 1
  • Julián Arévalo
    • 2
  • Jorge Blasco
    • 2
  • Nancy C. Andrés
    • 1
  • Jean C. Zenklusen
    • 3
  • Alejandro C. Curino
    • 1
  • María M. Facchinetti
    • 1
  1. 1.Laboratorio de Biología del CáncerInstituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB – CONICET), Centro Científico Tecnológico Bahía BlancaBahía BlancaArgentina
  2. 2.Servicio de Patología del Hospital Interzonal General de Agudos Dr José PennaBahía BlancaArgentina
  3. 3.Office of Cancer GenomicsNational Cancer Institute, National Institutes of HealthBethesdaUSA

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