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

• Published in: Journal of neuro-oncology Vol. 118; no. 1; pp. 49 - 60
• Main Authors: Salomón, Débora G., Fermento, María E., Gandini, Norberto A., Ferronato, María J., Arévalo, Julián, Blasco, Jorge, Andrés, Nancy C., Zenklusen, Jean C., Curino, Alejandro C., Facchinetti, María M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.05.2014; Springer Nature B.V
• Subjects: Adult; Age Factors; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Calcitriol - pharmacology; Calcium Channel Agonists - pharmacology; Cell Line, Tumor; Cell Movement - genetics; Cell Survival - drug effects; Cell Survival - physiology; Cyclin D1 - metabolism; Female; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Glioblastoma - metabolism; Glioblastoma - mortality; Glioblastoma - pathology; Humans; Laboratory Investigation; Male; Medicine; Medicine & Public Health; Middle Aged; Neurology; Oncogene Proteins - metabolism; Oncology; Receptors, Calcitriol - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Sex Factors; Time Factors; Tissue Array Analysis; Tissue microarray; Biomarker; Prognosis; Human GBM; Survival; Vitamin D receptor
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-014-1416-3

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 D 3 (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.