Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing
Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing using rabie...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 23, 2025
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| In: |
Cell
Year: 2025, Jahrgang: 188, Heft: 2, Pages: 390-411.e36 |
| ISSN: | 1097-4172 |
| DOI: | 10.1016/j.cell.2024.11.002 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cell.2024.11.002 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867424012765 
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| Verfasserangaben: | Svenja K. Tetzlaff, Ekin Reyhan, Nikolas Layer, C. Peter Bengtson, Alina Heuer, Julian Schroers, Anton J. Faymonville, Atefeh Pourkhalili Langeroudi, Nina Drewa, Elijah Keifert, Julia Wagner, Stella J. Soyka, Marc C. Schubert, Nirosan Sivapalan, Rangel L. Pramatarov, Verena Buchert, Tim Wageringel, Elena Grabis, Niklas Wißmann, Obada T. Alhalabi, Michael Botz, Jovana Bojcevski, Joaquín Campos, Berin Boztepe, Jonas G. Scheck, Sascha Henry Conic, Maria C. Puschhof, Giulia Villa, Richard Drexler, Yahya Zghaibeh, Fabian Hausmann, Sonja Hänzelmann, Matthia A. Karreman, Felix T. Kurz, Manuel Schröter, Marc Thier, Abigail K. Suwala, Karin Forsberg-Nilsson, Claudio Acuna, Julio Saez-Rodriguez, Amir Abdollahi, Felix Sahm, Michael O. Breckwoldt, Bogdana Suchorska, Franz L. Ricklefs, Dieter Henrik Heiland, and Varun Venkataramani |
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| 245 | 1 | 0 | |a Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing |c Svenja K. Tetzlaff, Ekin Reyhan, Nikolas Layer, C. Peter Bengtson, Alina Heuer, Julian Schroers, Anton J. Faymonville, Atefeh Pourkhalili Langeroudi, Nina Drewa, Elijah Keifert, Julia Wagner, Stella J. Soyka, Marc C. Schubert, Nirosan Sivapalan, Rangel L. Pramatarov, Verena Buchert, Tim Wageringel, Elena Grabis, Niklas Wißmann, Obada T. Alhalabi, Michael Botz, Jovana Bojcevski, Joaquín Campos, Berin Boztepe, Jonas G. Scheck, Sascha Henry Conic, Maria C. Puschhof, Giulia Villa, Richard Drexler, Yahya Zghaibeh, Fabian Hausmann, Sonja Hänzelmann, Matthia A. Karreman, Felix T. Kurz, Manuel Schröter, Marc Thier, Abigail K. Suwala, Karin Forsberg-Nilsson, Claudio Acuna, Julio Saez-Rodriguez, Amir Abdollahi, Felix Sahm, Michael O. Breckwoldt, Bogdana Suchorska, Franz L. Ricklefs, Dieter Henrik Heiland, and Varun Venkataramani |
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| 520 | |a Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing using rabies viruses to investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain, engaging in widespread functional communication, with cholinergic neurons driving glioblastoma invasion. We uncovered patient-specific and tumor-cell-state-dependent differences in synaptogenic gene expression associated with neuron-tumor connectivity and subsequent invasiveness. Importantly, radiotherapy enhanced neuron-tumor connectivity by increased neuronal activity. In turn, simultaneous neuronal activity inhibition and radiotherapy showed increased therapeutic effects, indicative of a role for neuron-to-glioma synapses in contributing to therapeutic resistance. Lastly, rabies-mediated genetic ablation of tumor-connected neurons halted glioblastoma progression, offering a viral strategy to tackle glioblastoma. Together, this study provides a framework to comprehensively characterize neuron-tumor networks and target glioblastoma. | ||
| 650 | 4 | |a brain tumor networks | |
| 650 | 4 | |a brain tumors | |
| 650 | 4 | |a cancer neuroscience | |
| 650 | 4 | |a glioblastoma | |
| 650 | 4 | |a invasion | |
| 650 | 4 | |a neuron-to-glioma synapse | |
| 650 | 4 | |a retrograde tracing | |
| 650 | 4 | |a therapeutic rabies virus | |
| 650 | 4 | |a therapeutic resistance | |
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