Glycation Interferes with the Expression of Sialyltransferases in Meningiomas

Meningiomas are the most common non-malignant intracranial tumors and prefer, like most tumors, anaerobic glycolysis for energy production (Warburg effect). This anaerobic glycolysis leads to an increased synthesis of the metabolite methylglyoxal (MGO) or glyoxal (GO), which is known to react with amino groups of proteins. This reaction is called glycation, thereby building advanced glycation end products (AGEs). In this study, we investigated the influence of glycation on sialylation in two meningioma cell lines, representing the WHO grade I (BEN-MEN-1) and the WHO grade III (IOMM-Lee). In the benign meningioma cell line, glycation led to differences in expression of sialyltransferases (ST3GAL1/2/3/5/6, ST6GAL1/2, ST6GALNAC2/6, and ST8SIA1/2), which are known to play a role in tumor progression. We could show that glycation of BEN-MEN-1 cells led to decreased expression of ST3Gal5. This resulted in decreased synthesis of the ganglioside GM3, the product of ST3Gal5. In the malignant meningioma cell line, we observed changes in expression of sialyltransferases (ST3GAL1/2/3, ST6GALNAC5, and ST8SIA1) after glycation, which correlates with less aggressive behavior.

Download Full-text

Glycation of benign meningioma cells leads to increased invasion

Biological Chemistry ◽

10.1515/hsz-2020-0376 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Philipp Selke ◽

Philip Rosenstock ◽

Kaya Bork ◽

Christian Strauss ◽

Rüdiger Horstkorte ◽

...

Keyword(s):

Cell Line ◽

Cell Lines ◽

Advanced Glycation Endproducts ◽

Malignant Cell ◽

Invasive Potential ◽

Benign Meningioma ◽

Who Grade ◽

Glycation Endproducts ◽

Men 1 ◽

Meningioma Cell

Abstract Meningiomas are the most common non-malignant intracranial tumors. Like most tumors, meningiomas prefer anaerobic glycolysis for energy production (Warburg effect). This leads to an increased synthesis of the metabolite methylglyoxal (MGO). This metabolite is known to react with amino groups of proteins. This reaction is called glycation, thereby building advanced glycation endproducts (AGEs). In this study, we investigated the influence of glycation on two meningioma cell lines, representing the WHO grade I (BEN-MEN-1) and the WHO grade III (IOMM-Lee). Increasing MGO concentrations led to the formation of AGEs and decreased growth in both cell lines. When analyzing the influence of glycation on adhesion, chemotaxis and invasion, we could show that the glycation of meningioma cells resulted in increased invasive potential of the benign meningioma cell line, whereas the invasive potential of the malignant cell line was reduced. In addition, glycation increased the E-cadherin- and decreased the N-cadherin-expression in BEN-MEN-1 cells, but did not affect the cadherin-expression in IOMM-Lee cells.

Download Full-text

Establishment of a benign meningioma cell line by hTERT-mediated immortalization

Laboratory Investigation ◽

10.1038/labinvest.3700307 ◽

2005 ◽

Vol 85 (9) ◽

pp. 1163-1171 ◽

Cited By ~ 65

Author(s):

Sylvia Püttmann ◽

Volker Senner ◽

Stephan Braune ◽

Beate Hillmann ◽

Rita Exeler ◽

...

Keyword(s):

Cell Line ◽

Benign Meningioma ◽

Meningioma Cell

Download Full-text

DDIS-34. HIGH-THROUGHPUT DRUG SCREENING OF FDA-APPROVED ANTINEOPLASTIC DRUGS FOR THE TREATMENT OF AGGRESSIVE MENINGIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noz175.285 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi70-vi70

Author(s):

Gerhard Jungwirth ◽

Tao Yu ◽

Fang Liu ◽

Rolf Warta ◽

Andreas Unterberg ◽

...

Keyword(s):

Cell Line ◽

Cell Lines ◽

High Throughput ◽

Drug Screening ◽

Antineoplastic Drugs ◽

Men 1 ◽

High Throughput Drug Screening ◽

Drug Concentrations ◽

Meningioma Cell ◽

The Impact

Abstract Currently, we are facing several challenges in the treatment of meningiomas: only subtotally removable tumors, high rate of recurrence in higher-grade meningiomas, malignancy, and lack of effective chemotherapeutic agents for aggressive or inoperable tumors. For these reasons, there is an urgent need for more successful treatments for aggressive meningiomas. Therefore, we used 147 FDA-approved antineoplastic drugs on two different meningioma cell lines, including the genetically modified cell line Ben-Men-1 (WHO°I) and the newly established anaplastic meningioma cell line NCH93 (WHO°III). The impact of the drugs on proliferation was assessed in a high-throughput 386-well format with CellTiter-Glo (Promega) and further validation was done by crystal-violet assay. Subsequent screening of 147 FDA-approved drugs resulted in the identification of potential 5 drugs, including Bortezomib, Carfilzomib, Omacetaxine, Paclitaxel, and Ponatinib. Dose-curve analysis revealed IC50 values of these drugs in the Ben-Men-1 and NCH93 cell lines as follows: Bortezomib 16.2 and 5.7 nM, Carfilzomib 4.8 and 2.6 nM, Omacetaxine and 5.0 and 8.9 nM, Paclitaxel 2.6 and 1.9 µM, and Ponatinib 278 and 206 nM. Inhibitor dosage of 10xIC50 values and higher lead to an average inhibition of Ben-Men-1 and NCH93 cells by up to 90% on day 2 (P< .001). The impact of the antineoplastic agents on the cell cycle was analyzed by flow cytometry. Percentages of sub-G1 phase were significantly elevated with increasing drug concentrations of all five tested compounds (P< .001). To assess the effects of the drugs on migration scratch assay was performed. Drug concentrations of 10xIC50 values resulted in an inhibition of migration in Ben-Men-1 cells for Bortezomib, Carfilzomib, and Omacetaxine by 49%, 30%, and 23%, respectively (P< .05). In conclusion, we identified 5 promising drugs for the treatment of aggressive meningiomas by applying a high-throughput drug screening of 147 FDA-approved antineoplastic drugs.

Download Full-text

Efficacy of decitabine in malignant meningioma cells: relation to promoter demethylation of distinct tumor suppressor and oncogenes and independence from TERT

Journal of Neurosurgery ◽

10.3171/2020.7.jns193097 ◽

2020 ◽

pp. 1-10

Author(s):

Louise Stögbauer ◽

Christian Thomas ◽

Andrea Wagner ◽

Nils Warneke ◽

Eva Christine Bunk ◽

...

Keyword(s):

Dna Methylation ◽

Tumor Suppressor ◽

Promoter Methylation ◽

Tumor Suppressor Genes ◽

Telomerase Activity ◽

High Grade ◽

Htert Promoter ◽

Men 1 ◽

Meningioma Cell ◽

Tert Expression

OBJECTIVEChemotherapeutic options for meningiomas refractory to surgery or irradiation are largely unknown. Human telomerase reverse transcriptase (hTERT) promoter methylation with subsequent TERT expression and telomerase activity, key features in oncogenesis, are found in most high-grade meningiomas. Therefore, the authors investigated the impact of the demethylating agent decitabine (5-aza-2ʹ-deoxycytidine) on survival and DNA methylation in meningioma cells.METHODShTERT promoter methylation, telomerase activity, TERT expression, and cell viability and proliferation were investigated prior to and after incubation with decitabine in two benign (HBL-52 and Ben-Men 1) and one malignant (IOMM-Lee) meningioma cell line. The global effects of decitabine on DNA methylation were additionally explored with DNA methylation profiling.RESULTSHigh levels of TERT expression, telomerase activity, and hTERT promoter methylation were found in IOMM-Lee and Ben-Men 1 but not in HBL-52 cells. Decitabine induced a dose-dependent significant decrease of proliferation and viability after incubation with doses from 1 to 10 μM in IOMM-Lee but not in HBL-52 or Ben-Men 1 cells. However, effects in IOMM-Lee cells were not related to TERT expression, telomerase activity, or hTERT promoter methylation. Genome-wide methylation analyses revealed distinct demethylation of 14 DNA regions after drug administration in the decitabine-sensitive IOMM-Lee but not in the decitabine-resistant HBL-52 cells. Differentially methylated regions covered promoter regions of 11 genes, including several oncogenes and tumor suppressor genes that to the authors’ knowledge have not yet been described in meningiomas.CONCLUSIONSDecitabine decreases proliferation and viability in high-grade but not in benign meningioma cell lines. The effects of decitabine are TERT independent but related to DNA methylation changes of promoters of distinct tumor suppressor genes and oncogenes.

Download Full-text