gms | German Medical Science

66th Annual Meeting of the German Society of Neurosurgery (DGNC)
Friendship Meeting with the Italian Society of Neurosurgery (SINch)

German Society of Neurosurgery (DGNC)

7 - 10 June 2015, Karlsruhe

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Comparative analysis of stem cell markers in matched primary and recurrent glioblastomas

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  • Charlotte Flüh - Klinik für Neurochirurgie, UKSH, Campus Kiel, Deutschland
  • Kirsten Hattermann - Anatomisches Institut, CAU zu Kiel, Deutschland
  • Hubertus Maximilian Mehdorn - Klinik für Neurochirurgie, UKSH, Campus Kiel, Deutschland
  • Rolf Mentlein - Anatomisches Institut, CAU zu Kiel, Deutschland
  • Janka Held-Feindt - Klinik für Neurochirurgie, UKSH, Campus Kiel, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Karlsruhe, 07.-10.06.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocP 049

doi: 10.3205/15dgnc447, urn:nbn:de:0183-15dgnc4477

Published: June 2, 2015

© 2015 Flüh et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Glioblastomas show a complex multitude of cells with various differentiation levels. In this variety, cells with stem cell properties seem to massively influence tumor malignancy. However, comparative studies of stem cell markers on primary WHO grade IV glioblastomas versus relapses are currently not available. Therefore, our study investigates the expression profile of different neural and embryonal stem cell markers in matched primary and recurrent glioblastomas, analyzes their coexpression with two chemokine receptors (CXCR4 and CXCR7) as functional markers of tumor differentiation in situ and evaluates the effect of chemotherapy on transcriptional gene regulation in vitro.

Method: We analyzed the expression profile of different stem cell markers in 11 matched primary and recurrent glioblastomas by qPCR and double-immunofluorescence staining. The number of cells positively stained for Oct4, Klf4 and Sox2 was counted in 3 matched pairs of primary versus relapse glioblastomas costained for CXCR4 and CXCR7. In addition, we examined the influence of temozolomide and camptothecin on stem cell marker expression by qPCR.

Results: The expression of the neural stem cell markers Musashi-1 (p<0.01), c-myc (p<0.001), Oct4 (p<0.05), Nanog (p<0.05) and the chemokine receptor CXCR7 (p<0.01) decreases in recurrent glioblastomas compared to primary glioblastomas. No alteration was seen for Sox2, Klf4 and CXCR4. These results were in line with quantitative analysis in situ. In addition, we observed an upregulation of expression of Klf4 (p24h<0.01, p48h<0.001) and Oct4 (p48h<0.01) by temozolomide and by camptothecin (Oct4: p24h<0.01; Klf4: p24h, 48h<0.01) in T98G cells. Analysis of A172 cells also suggested upregulation of Klf4 by temozolomide and camptothecin (p48h<0.01).

Conclusions: Stem cell markers are involved in tumor progression of glioblastomas in a complex way. Chemotherapy has an effect on their transcriptional regulation. As neural stem cell markers are key structures for the differentiation of glioblastoma cells, this implies a potential role concerning prognosis and receptivity for chemotherapy in practice.