Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells
Sarah Rehbein1, Anna-Lena Possmayer1, Süleyman Bozkurt2
1Experimental Neurosurgery, Department of Neurosurgery, Neuroscience Center, Goethe University Hospital, 60596 Frankfurt am Main, Germany.
Abstract:
Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis. These and other factors are hypothesized to be largely due to the fact that glioblastoma cells are known to be able to obtain stem-like traits, thereby driving these phenotypes. Recently, we have shown that the in vitro and ex vivo treatment of glioblastoma stem-like cells with the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2-vitamin D3) can block stemness in a subset of cell lines and reduce tumor growth. Here, we expanded our cell panel to over 40 different cultures and can show that, while half of the tested cell lines are sensitive, a quarter can be classified as high responders. Using genetic and proteomic analysis, we further determined that treatment success can be partially explained by specific polymorphism of the vitamin D3 receptor and that high responders display a proteome suggestive of blockade of stemness, as well as migratory potential.
Insights
Vitamin D3 (calcitriol) can block cancer stemness and reduce tumor growth in glioblastoma. Genetic factors and specific vitamin D3 receptor variations influence treatment effectiveness, particularly in high-responder glioblastoma cells.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Endocrinology
Background:
- Glioblastoma is an aggressive brain cancer with poor prognosis and high recurrence rates.
- Glioblastoma stem-like cells are implicated in treatment resistance and tumor progression.
- Limited effective therapeutic strategies exist for glioblastoma.
Purpose of the Study:
- To investigate the efficacy of calcitriol (active vitamin D3) in targeting glioblastoma stemness.
- To identify factors influencing response to calcitriol treatment in a large panel of glioblastoma cell lines.
- To explore the genetic and proteomic basis for calcitriol sensitivity and resistance.
Main Methods:
- Treatment of over 40 glioblastoma cell lines with calcitriol (1α,25(OH)2-vitamin D3).
- Assessment of cell line sensitivity and response levels (sensitive, high responders).
- Genetic and proteomic analyses to identify predictive biomarkers and mechanisms of action.
Main Results:
- Calcitriol treatment demonstrated efficacy in blocking stemness and reducing tumor growth in a subset of glioblastoma cell lines.
- Approximately half of the tested cell lines were sensitive to calcitriol, with a quarter classified as high responders.
- Vitamin D3 receptor (VDR) polymorphisms partially explained treatment success; high responders showed proteomic signatures of blocked stemness and reduced migration.
Conclusions:
- Calcitriol is a potential therapeutic agent for glioblastoma, particularly effective in sensitive cell lines.
- Vitamin D3 receptor genetics and proteomic profiles are key determinants of calcitriol efficacy in glioblastoma.
- Targeting glioblastoma stemness with vitamin D3 analogs warrants further investigation for improved cancer therapy.
More Related Videos
09:36Live-Cell Imaging Assays to Study Glioblastoma Brain Tumor Stem Cell Migration and Invasion
Published on: August 29, 2018
12:25Optimization of High Grade Glioma Cell Culture from Surgical Specimens for Use in Clinically Relevant Animal Models and 3D Immunochemistry
Published on: January 7, 2014