Retinoids inhibit human glioma cell proliferation and migration in primary cell cultures but not in established cell lines
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Updated: Oct 17, 2026
Establishment and Propagation of Human Retinoblastoma Tumors in Immune Deficient Mice
Published on: August 4, 2011
1Department of Neurosurgery, University of Würzburg, Germany.
Objective:
Retinoids are known to exhibit a broad spectrum of biological activities, and they participate in the onset of differentiation and the inhibition of growth in a wide variety of cancer cells. Some of these vitamin A derivatives are already in clinical use. However, data on retinoid actions in glial tumors are rather sparse. Therefore, we studied the effects of the natural retinoic acid (RA) forms all-trans-RA, 9-cis-RA, and 13-cis-RA on glioma cell lines and primary cultures from patients with glioblastomas multiforme.
Methods:
Six human glioma cell lines, one rat glioma cell line, and 20 primary cultures established from biopsies from patients with glioblastomas multiforme were investigated. Tumor cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell-counting assays. Random migration out of tumor spheroids was quantified using a video-morphometry system. Invasion was investigated using a confrontational coculture test system. Retinoid receptor (RA receptor [RAR]alpha, -beta, and -gamma and retinoid X receptor [RXR]alpha, -beta, and -gamma) expression status was determined using reverse transcription-polymerase chain reaction studies.
Results:
Treatment of five human glioma cell lines with the different retinoids at concentrations up to 10(-5) mol/L produced no reduction of proliferation, using various incubation times. For one human glioma cell line (U343MG-A) and one rat glioma cell line (C6), which were previously reported to be sensitive to retinoids, we could confirm strong inhibitory effects on proliferation and clear changes in morphological features after retinoid treatment. Application of the different retinoids to low-passage primary cultures of human glioblastomas resulted in marked inhibition of proliferation (30-95%) for all tested samples. Using three-dimensional spheroid cultures, we detected retinoid-induced decreases in cell migration (24-65%). Invasion was not affected by these vitamin A derivatives. In an analysis of the expression patterns for retinoid receptors (RARs and RXRs), all primary culture samples yielded positive results for RAR gamma and RXR alpha and negative results for RAR alpha, RAR beta, and RXR gamma, whereas the results of RXR beta expression were heterogeneous among different patients. The cell lines, irrespective of their RA sensitivities, did not exhibit any major differences in receptor expression.
Conclusion:
Retinoids strongly inhibit proliferation and migration in primary cultures of human glioblastomas multiforme. Our data support a clinical trial of retinoids for the treatment of human malignant gliomas. We observed that most established cell lines were not sensitive to RA. This difference between long-term cell lines and primary cultures cannot be explained by different retinoid receptor expression patterns.
Insights
Retinoids significantly inhibit proliferation and migration in primary glioblastoma cultures, suggesting potential for treating malignant gliomas. Most established cell lines showed no sensitivity to retinoic acid (RA).
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Retinoids, vitamin A derivatives, possess known anti-cancer properties, including differentiation induction and growth inhibition.
- Limited data exists on retinoid efficacy in glial tumors, necessitating further investigation.
Purpose of the Study:
- To investigate the effects of natural retinoic acid (RA) forms on glioma cell lines and primary glioblastoma cultures.
- To assess retinoid impact on proliferation, migration, and invasion.
Main Methods:
- Utilized six human and one rat glioma cell lines, plus 20 primary glioblastoma cultures.
- Assessed proliferation, migration (video-morphometry), and invasion (coculture system).
- Determined retinoid receptor (RAR, RXR) expression via RT-PCR.
Main Results:
- Retinoids inhibited proliferation (30-95%) and migration (24-65%) in primary glioblastoma cultures but not most cell lines.
- Invasion remained unaffected by retinoid treatment.
- Primary cultures showed consistent RAR gamma and RXR alpha expression, unlike cell lines.
Conclusions:
- Retinoids demonstrate potent anti-proliferative and anti-migratory effects on primary human glioblastomas.
- Findings support clinical trials of retinoids for malignant glioma treatment.
- Discrepancies in retinoid sensitivity between cell lines and primary cultures warrant further study.
