Epithelial-to-mesenchymal transition in paired human primary and recurrent glioblastomas

  • Authors:
    • Carolin Kubelt
    • Kirsten Hattermann
    • Susanne Sebens
    • H. Maximilian Mehdorn
    • Janka Held-Feindt
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  • Published online on: March 31, 2015     https://doi.org/10.3892/ijo.2015.2944
  • Pages: 2515-2525
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Abstract

Patients with highly malignant glioblastomas have a short median survival time mainly due to aggressive relapses after therapeutic treatment. Beside others, they achieve their progressive character via epithelial-to-mesenchymal transition (EMT). However, comprehensive investigations on EMT in paired primary-recurrent glioblastoma pairs are presently not available. Thus, in our present study we examined the expression profile of different EMT-markers in 17 matched primary and recurrent glioblastomas by qPCR and double-immunofluorescence stainings to identify EMT marker expressing cell types. Additionally, we analyzed the influence of temozolomide on EMT marker expression in vitro. In comparison to primary tumors, expression of β-catenin (p<0.05), Snail1 (p<0.05), Snail2/Slug (p<0.05), biglycan (p<0.05) and Twist1 (p<0.01) was downregulated in recurrence whereas L1CAM showed upregulation (p<0.05; qPCR). Expression of desmoplakin, vimentin, fibronectin and TGF-β1 with its receptors TGF-βR1 and TGF-βR2 was almost unchanged. Comparing each individual pair, five different ‘EMT groups’ within our glioblastoma collective were identified according to the regulation of mRNA expression of GFAP, desmoplakin, Snail1, Snail2, Twist1 and vimentin. Additionally, double-stainings of EMT markers in combination with cell specific markers (glial fibrillary acidic protein, CD11b, von Willebrand factor) revealed that EMT markers were expressed in a complex pattern with all three cellular types as possible sources. Temozolomide treatment significantly induced mRNA expression of nearly all investigated EMT markers in T98G glioma cells. Thus, EMT seems to be involved in glioma progression in a complex way requiring an individualized analysis, and is influenced by commonly used therapeutic options in glioma therapy.
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June-2015
Volume 46 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kubelt C, Hattermann K, Sebens S, Mehdorn HM and Held-Feindt J: Epithelial-to-mesenchymal transition in paired human primary and recurrent glioblastomas. Int J Oncol 46: 2515-2525, 2015.
APA
Kubelt, C., Hattermann, K., Sebens, S., Mehdorn, H.M., & Held-Feindt, J. (2015). Epithelial-to-mesenchymal transition in paired human primary and recurrent glioblastomas. International Journal of Oncology, 46, 2515-2525. https://doi.org/10.3892/ijo.2015.2944
MLA
Kubelt, C., Hattermann, K., Sebens, S., Mehdorn, H. M., Held-Feindt, J."Epithelial-to-mesenchymal transition in paired human primary and recurrent glioblastomas". International Journal of Oncology 46.6 (2015): 2515-2525.
Chicago
Kubelt, C., Hattermann, K., Sebens, S., Mehdorn, H. M., Held-Feindt, J."Epithelial-to-mesenchymal transition in paired human primary and recurrent glioblastomas". International Journal of Oncology 46, no. 6 (2015): 2515-2525. https://doi.org/10.3892/ijo.2015.2944