PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells
Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/20/11126 |
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| author | Carolin Seifert Ellen Balz Susann Herzog Anna Korolev Sebastian Gaßmann Heiko Paland Matthias A. Fink Markus Grube Sascha Marx Gabriele Jedlitschky Mladen V. Tzvetkov Bernhard H. Rauch Henry W. S. Schroeder Sandra Bien-Möller |
| author_facet | Carolin Seifert Ellen Balz Susann Herzog Anna Korolev Sebastian Gaßmann Heiko Paland Matthias A. Fink Markus Grube Sascha Marx Gabriele Jedlitschky Mladen V. Tzvetkov Bernhard H. Rauch Henry W. S. Schroeder Sandra Bien-Möller |
| author_sort | Carolin Seifert |
| collection | DOAJ |
| description | Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research. We have previously demonstrated that PIM1 is involved in survival of GBM cells and in GBM growth in a mouse model. However, little is known about the importance of PIM1 in cancer stem cells. Here, we report on the role of PIM1 in GBM stem cell behavior and killing. PIM1 inhibition negatively regulates the protein expression of the stem cell markers CD133 and Nestin in GBM cells (LN-18, U-87 MG). In contrast, CD44 and the astrocytic differentiation marker GFAP were up-regulated. Furthermore, PIM1 expression was increased in neurospheres as a model of GBM stem-like cells. Treatment of neurospheres with PIM1 inhibitors (TCS PIM1-1, Quercetagetin, and LY294002) diminished the cell viability associated with reduced DNA synthesis rate, increased caspase 3 activity, decreased PCNA protein expression, and reduced neurosphere formation. Our results indicate that PIM1 affects the glioblastoma stem cell behavior, and its inhibition kills glioblastoma stem-like cells, pointing to PIM1 targeting as a potential anti-glioblastoma therapy. |
| first_indexed | 2024-03-10T06:30:52Z |
| format | Article |
| id | doaj.art-84b52da1c50b4d37b01a635ce11459f2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:30:52Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-84b52da1c50b4d37b01a635ce11459f22023-11-22T18:34:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201112610.3390/ijms222011126PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like CellsCarolin Seifert0Ellen Balz1Susann Herzog2Anna Korolev3Sebastian Gaßmann4Heiko Paland5Matthias A. Fink6Markus Grube7Sascha Marx8Gabriele Jedlitschky9Mladen V. Tzvetkov10Bernhard H. Rauch11Henry W. S. Schroeder12Sandra Bien-Möller13Department of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurosurgery, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurosurgery, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Pharmacology, University Medicine Greifswald, 17489 Greifswald, GermanyDespite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research. We have previously demonstrated that PIM1 is involved in survival of GBM cells and in GBM growth in a mouse model. However, little is known about the importance of PIM1 in cancer stem cells. Here, we report on the role of PIM1 in GBM stem cell behavior and killing. PIM1 inhibition negatively regulates the protein expression of the stem cell markers CD133 and Nestin in GBM cells (LN-18, U-87 MG). In contrast, CD44 and the astrocytic differentiation marker GFAP were up-regulated. Furthermore, PIM1 expression was increased in neurospheres as a model of GBM stem-like cells. Treatment of neurospheres with PIM1 inhibitors (TCS PIM1-1, Quercetagetin, and LY294002) diminished the cell viability associated with reduced DNA synthesis rate, increased caspase 3 activity, decreased PCNA protein expression, and reduced neurosphere formation. Our results indicate that PIM1 affects the glioblastoma stem cell behavior, and its inhibition kills glioblastoma stem-like cells, pointing to PIM1 targeting as a potential anti-glioblastoma therapy.https://www.mdpi.com/1422-0067/22/20/11126glioblastomaPIM1 kinasestem-like cellsneurospheres |
| spellingShingle | Carolin Seifert Ellen Balz Susann Herzog Anna Korolev Sebastian Gaßmann Heiko Paland Matthias A. Fink Markus Grube Sascha Marx Gabriele Jedlitschky Mladen V. Tzvetkov Bernhard H. Rauch Henry W. S. Schroeder Sandra Bien-Möller PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells International Journal of Molecular Sciences glioblastoma PIM1 kinase stem-like cells neurospheres |
| title | PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells |
| title_full | PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells |
| title_fullStr | PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells |
| title_full_unstemmed | PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells |
| title_short | PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells |
| title_sort | pim1 inhibition affects glioblastoma stem cell behavior and kills glioblastoma stem like cells |
| topic | glioblastoma PIM1 kinase stem-like cells neurospheres |
| url | https://www.mdpi.com/1422-0067/22/20/11126 |
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