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Hannen, R.* ; Selmansberger, M. ; Hauswald, M.* ; Pagenstecher, A.* ; Nist, A.* ; Stiewe, T.* ; Acker, T.* ; Carl, B.* ; Nimsky, C.* ; Bartsch, J.W.*

Comparative transcriptomic analysis of temozolomide resistant primary GBM stem-like cells and recurrent GBM identifies up-regulation of the carbonic anhydrase CA2 gene as resistance factor.

Cancers 11:921 (2019)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
About 95% of patients with Glioblastoma (GBM) show tumor relapse, leaving them with limited therapeutic options as recurrent tumors are most often resistant to the first line chemotherapy standard Temozolomide (TMZ). To identify molecular pathways involved in TMZ resistance, primary GBM Stem-like Cells (GSCs) were isolated, characterized, and selected for TMZ resistance in vitro. Subsequently, RNA sequencing analysis was performed and revealed a total of 49 differentially expressed genes (|log2-fold change| > 0.5 and adjusted p-value < 0.1) in TMZ resistant stem-like cells compared to their matched DMSO control cells. Among up-regulated genes, we identified carbonic anhydrase 2 (CA2) as a candidate gene correlated with glioma malignancy and patient survival. Notably, we describe consistent up-regulation of CA2 not only in TMZ resistant GSCs on mRNA and protein level, but also in patient-matched clinical samples of first manifest and recurrent tumors. Co-treatment with the carbonic anhydrase inhibitor Acetazolamid (ACZ) sensitized cells to TMZ induced cell death. Cumulatively, our findings illustrate the potential of CA2 as a chemosensitizing target in recurrent GBM and provide a rationale for a therapy associated inhibition of CA2 to overcome TMZ induced chemoresistance.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Glioblastoma ; Gbm Stem-like Cells ; Temozolomide ; Chemoresistance ; Gbm Recurrence ; Transcriptomics ; Acetazolamide ; Carbonic Anhydrase 2; Msh6 Mutations; Glioblastoma; Evolution; Radiotherapy; Therapy; Gliomas; Ix
ISSN (print) / ISBN 2072-6694
Zeitschrift Cancers
Quellenangaben Band: 11, Heft: 7, Seiten: , Artikelnummer: 921 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Translational Metabolic Oncology (IDC-TMO)