Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy

Helweg L, Storm J, Witte K, Schulten W, Wrachtrup L, Janotte T, Kitke A, Greiner J, Knabbe C, Kaltschmidt B, Simon M, et al. (2022)
International Journal of Molecular Sciences 23(21): 12919.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
Glioblastoma multiforme (GBM) is the most aggressive and most common malignant brain tumor with poor patient survival despite therapeutic intervention. On the cellular level, GBM comprises a rare population of glioblastoma stem cells (GSCs), driving therapeutic resistance, invasion, and recurrence. GSCs have thus come into the focus of therapeutic strategies, although their targeting remains challenging. In the present study, we took advantage of three GSCs-populations recently established in our lab to investigate key signaling pathways and subsequent therapeutic strategies targeting GSCs. We observed that NF-κB, a crucial transcription factor in GBM progression, was expressed in all CD44+/CD133+/Nestin+-GSC-populations. Exposure to TNFα led to activation of NF-κB-RELA and/or NF-κB-c-REL, depending on the GBM type. GSCs further expressed the proto-oncogene MYC family, with MYChigh GSCs being predominantly located in the tumor spheres (“GROW”-state) while NF-κB-RELAhigh GSCs were migrating out of the sphere (“GO”-state). We efficiently targeted GSCs by the pharmacologic inhibition of NF-κB using PTDC/Bortezomib or inhibition of MYC by KJ-Pyr-9, which significantly reduced GSC-viability, even in comparison to the standard chemotherapeutic drug temozolomide. As an additional cell-therapeutic strategy, we showed that NK cells could kill GSCs. Our findings offer new perspectives for developing efficient patient-specific chemo- and immunotherapy against GBM.
Stichworte
glioblastoma multiforme; cancer stem cells; NF-κB; MYC; NK-cells; chemotherapy; immunotherapy
Erscheinungsjahr
2022
Zeitschriftentitel
International Journal of Molecular Sciences
Band
23
Ausgabe
21
Art.-Nr.
12919
eISSN
1422-0067
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2966641

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Helweg L, Storm J, Witte K, et al. Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy. International Journal of Molecular Sciences. 2022;23(21): 12919.
Helweg, L., Storm, J., Witte, K., Schulten, W., Wrachtrup, L., Janotte, T., Kitke, A., et al. (2022). Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy. International Journal of Molecular Sciences, 23(21), 12919. https://doi.org/10.3390/ijms232112919
Helweg, Laureen, Storm, Jonathan, Witte, Kaya, Schulten, Wiebke, Wrachtrup, Lennart, Janotte, Till, Kitke, Angelika, et al. 2022. “Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy”. International Journal of Molecular Sciences 23 (21): 12919.
Helweg, L., Storm, J., Witte, K., Schulten, W., Wrachtrup, L., Janotte, T., Kitke, A., Greiner, J., Knabbe, C., Kaltschmidt, B., et al. (2022). Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy. International Journal of Molecular Sciences 23:12919.
Helweg, L., et al., 2022. Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy. International Journal of Molecular Sciences, 23(21): 12919.
L. Helweg, et al., “Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy”, International Journal of Molecular Sciences, vol. 23, 2022, : 12919.
Helweg, L., Storm, J., Witte, K., Schulten, W., Wrachtrup, L., Janotte, T., Kitke, A., Greiner, J., Knabbe, C., Kaltschmidt, B., Simon, M., Kaltschmidt, C.: Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy. International Journal of Molecular Sciences. 23, : 12919 (2022).
Helweg, Laureen, Storm, Jonathan, Witte, Kaya, Schulten, Wiebke, Wrachtrup, Lennart, Janotte, Till, Kitke, Angelika, Greiner, Johannes, Knabbe, Cornelius, Kaltschmidt, Barbara, Simon, Matthias, and Kaltschmidt, Christian. “Targeting Key Signaling Pathways in Glioblastoma Stem Cells for the Development of Efficient Chemo- and Immunotherapy”. International Journal of Molecular Sciences 23.21 (2022): 12919.
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2022-11-17T08:48:44Z
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