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Assessment of genetic markers and glioblastoma stem-like cells in activation of dendritic cells

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Abstract

Glioblastoma (GBM) is the most common and aggressive intraparenchymal primary brain tumor in adults. The principal reasons for the poor outcomes of GBM are the high rates of recurrence and resistance to chemotherapy. The aim of this study was to determine the role of tailored cellular therapy for GBM with a poor prognosis and compare the activity of dendritic cells (DCs) that have encountered GBM cells. Detecting the correlations between methylation and expression of MGMT and PTEN genes and GBM cancer stem cells (CSCs) markers after co-cultures with a mononuclear cell cocktail are also aims for this study. Allogenic umbilical cord blood (UCB)-derived DCs were labeled with the CD11a and CD123 for immature DCs, and CD80 and CD11c for mature DCs. CD34, CD45, and CD56 cells were isolated from allogenic UCB for using in DCs maturation. GBM CSCs were detected with CD133/1 and CD111 antibodies after co-culture studies. DC activation was carried out via GBM cells including CD133 and CD111 cells and a mononuclear cells cocktail including CD34, CD45, and CD56 natural killer cells. Real-time PCR was performed to detect the expression and promoter methylation status of PTEN and MGMT genes. The expression of CSCs markers was found in all GBM cases, and a statistically significant correlation was found among them after co-culture studies. The most pronounced affinity of DCs to GBM cells was observed at dilutions between 1/4 and 1/256 in co-cultures. There was a statistically significant correlation between cellularity and granularity ratios for CD123 and CD11c. PTEN and MGMT gene expression and methylation values were evaluated with respect to CSCs expression and no statistical significance was found. Activation of DCs might associate with CSCs and the mononuclear cells cocktail including CD34, CD45, and CD56 cells which were obtained from allogenic UCB.

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Acknowledgments

This study was supported by ONKIM Stem Cell Technologies. We acknowledge Pınar Hüner and Cem Kulen from ONKIM Stem Cell Technologies for their contributions in the study.

Conflict of interest

We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. We do not have any conflict of interest.

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Authors and Affiliations

  1. Cancer Research Center, Ege University, Bornova, 35100, Izmir, Turkey

    Aysel Yurtsever, Ayfer Haydaroglu & Gul Kitapcioglu

  2. Department of Medical Biology, Ege University Medical Faculty, Bornova, 35100, Izmir, Turkey

    Cigir Biray Avci & Cumhur Gunduz

  3. Neurosurgery Department, Ege University Medical Faculty, Bornova, 35100, Izmir, Turkey

    Nezih Oktar & Tayfun Dalbasti

  4. Department of Stem Cell, EU Health Science Institute, Bornova, 35100, Izmir, Turkey

    Hasan Onur Caglar

  5. Department of Obstetrics and Gynecology, Yeditepe University Hospital, 34752, Kozyatagi/Istanbul, Turkey

    Rukset Attar

  6. Biostatistics and Medical Informatics Department, Ege University Medical Faculty, Bornova, 35100, Izmir, Turkey

    Gul Kitapcioglu

Authors
  1. Aysel Yurtsever
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  2. Ayfer Haydaroglu
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  3. Cigir Biray Avci
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  4. Cumhur Gunduz
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  5. Nezih Oktar
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  6. Tayfun Dalbasti
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  7. Hasan Onur Caglar
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  8. Rukset Attar
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  9. Gul Kitapcioglu
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Correspondence to Cigir Biray Avci.

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Yurtsever, A., Haydaroglu, A., Biray Avci, C. et al. Assessment of genetic markers and glioblastoma stem-like cells in activation of dendritic cells. Human Cell 26, 105–113 (2013). https://doi.org/10.1007/s13577-013-0065-8

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  • DOI: https://doi.org/10.1007/s13577-013-0065-8

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