Glycation Leads to Increased Invasion of Glioblastoma Cells
Glioblastoma (GBM) is a highly aggressive and invasive brain tumor with a poor prognosis despite extensive treatment. The switch to aerobic glycolysis, known as the Warburg effect, in cancer cells leads to an increased production of methylglyoxal (MGO), a potent glycation agent with pro-tumorigenic...
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/9/1219 |
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| author | Paola Schildhauer Philipp Selke Christian Scheller Christian Strauss Rüdiger Horstkorte Sandra Leisz Maximilian Scheer |
| author_facet | Paola Schildhauer Philipp Selke Christian Scheller Christian Strauss Rüdiger Horstkorte Sandra Leisz Maximilian Scheer |
| author_sort | Paola Schildhauer |
| collection | DOAJ |
| description | Glioblastoma (GBM) is a highly aggressive and invasive brain tumor with a poor prognosis despite extensive treatment. The switch to aerobic glycolysis, known as the Warburg effect, in cancer cells leads to an increased production of methylglyoxal (MGO), a potent glycation agent with pro-tumorigenic characteristics. MGO non-enzymatically reacts with proteins, DNA, and lipids, leading to alterations in the signaling pathways, genomic instability, and cellular dysfunction. In this study, we investigated the impact of MGO on the LN229 and U251 (WHO grade IV, GBM) cell lines and the U343 (WHO grade III) glioma cell line, along with primary human astrocytes (hA). The results showed that increasing concentrations of MGO led to glycation, the accumulation of advanced glycation end-products, and decreasing cell viability in all cell lines. The invasiveness of the GBM cell lines increased under the influence of physiological MGO concentrations (0.3 mmol/L), resulting in a more aggressive phenotype, whereas glycation decreased the invasion potential of hA. In addition, glycation had differential effects on the ECM components that are involved in the invasion progress, upregulating TGFβ, brevican, and tenascin C in the GBM cell lines LN229 and U251. These findings highlight the importance of further studies on the prevention of glycation through MGO scavengers or glyoxalase 1 activators as a potential therapeutic strategy against glioma and GBM. |
| first_indexed | 2024-03-11T04:22:22Z |
| format | Article |
| id | doaj.art-8872e17904fa4f42a8d46896afc62304 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T04:22:22Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8872e17904fa4f42a8d46896afc623042023-11-17T22:42:56ZengMDPI AGCells2073-44092023-04-01129121910.3390/cells12091219Glycation Leads to Increased Invasion of Glioblastoma CellsPaola Schildhauer0Philipp Selke1Christian Scheller2Christian Strauss3Rüdiger Horstkorte4Sandra Leisz5Maximilian Scheer6Department of Neurosurgery, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin-Luther-University Halle-Wittenberg, 06114 Halle (Saale), GermanyDepartment of Neurosurgery, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyDepartment of Neurosurgery, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin-Luther-University Halle-Wittenberg, 06114 Halle (Saale), GermanyDepartment of Neurosurgery, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyDepartment of Neurosurgery, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyGlioblastoma (GBM) is a highly aggressive and invasive brain tumor with a poor prognosis despite extensive treatment. The switch to aerobic glycolysis, known as the Warburg effect, in cancer cells leads to an increased production of methylglyoxal (MGO), a potent glycation agent with pro-tumorigenic characteristics. MGO non-enzymatically reacts with proteins, DNA, and lipids, leading to alterations in the signaling pathways, genomic instability, and cellular dysfunction. In this study, we investigated the impact of MGO on the LN229 and U251 (WHO grade IV, GBM) cell lines and the U343 (WHO grade III) glioma cell line, along with primary human astrocytes (hA). The results showed that increasing concentrations of MGO led to glycation, the accumulation of advanced glycation end-products, and decreasing cell viability in all cell lines. The invasiveness of the GBM cell lines increased under the influence of physiological MGO concentrations (0.3 mmol/L), resulting in a more aggressive phenotype, whereas glycation decreased the invasion potential of hA. In addition, glycation had differential effects on the ECM components that are involved in the invasion progress, upregulating TGFβ, brevican, and tenascin C in the GBM cell lines LN229 and U251. These findings highlight the importance of further studies on the prevention of glycation through MGO scavengers or glyoxalase 1 activators as a potential therapeutic strategy against glioma and GBM.https://www.mdpi.com/2073-4409/12/9/1219glycationinvasionglioblastomagliomaastrocytesmethylglyoxal |
| spellingShingle | Paola Schildhauer Philipp Selke Christian Scheller Christian Strauss Rüdiger Horstkorte Sandra Leisz Maximilian Scheer Glycation Leads to Increased Invasion of Glioblastoma Cells Cells glycation invasion glioblastoma glioma astrocytes methylglyoxal |
| title | Glycation Leads to Increased Invasion of Glioblastoma Cells |
| title_full | Glycation Leads to Increased Invasion of Glioblastoma Cells |
| title_fullStr | Glycation Leads to Increased Invasion of Glioblastoma Cells |
| title_full_unstemmed | Glycation Leads to Increased Invasion of Glioblastoma Cells |
| title_short | Glycation Leads to Increased Invasion of Glioblastoma Cells |
| title_sort | glycation leads to increased invasion of glioblastoma cells |
| topic | glycation invasion glioblastoma glioma astrocytes methylglyoxal |
| url | https://www.mdpi.com/2073-4409/12/9/1219 |
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