Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases their Susceptibility to Temozolomide

Version 1 : Received: 27 June 2021 / Approved: 29 June 2021 / Online: 29 June 2021 (08:37:43 CEST)

A peer-reviewed article of this Preprint also exists.

Gerstmeier, J.; Possmayer, A.-L.; Bozkurt, S.; Hoffmann, M.E.; Dikic, I.; Herold-Mende, C.; Burger, M.C.; Münch, C.; Kögel, D.; Linder, B. Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide. Cancers 2021, 13, 3577. Gerstmeier, J.; Possmayer, A.-L.; Bozkurt, S.; Hoffmann, M.E.; Dikic, I.; Herold-Mende, C.; Burger, M.C.; Münch, C.; Kögel, D.; Linder, B. Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide. Cancers 2021, 13, 3577.

Journal reference: Cancers 2021, 13, 3577
DOI: 10.3390/cancers13143577

Abstract

: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

Subject Areas

Calcitriol; Vitamin D3; Glioblastoma; Glioblastoma stem-like cells

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