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

Kubelt,Carolin; Hattermann,Kirsten; Sebens,Susanne; Mehdorn,H. Maximilian; Held-Feindt,Janka

doi:10.3892/ijo.2015.2944

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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Affiliations: Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany, Department of Anatomy, University of Kiel, D-24118 Kiel, Germany, Institute for Experimental Medicine, Inflammatory Carcinogenesis, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany
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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