| Autor: |
Cathy Pichol-Thievend, Oceane Anezo, Aafrin M. Pettiwala, Guillaume Bourmeau, Remi Montagne, Anne-Marie Lyne, Pierre-Olivier Guichet, Pauline Deshors, Alberto Ballestín, Benjamin Blanchard, Juliette Reveilles, Vidhya M. Ravi, Kevin Joseph, Dieter H. Heiland, Boris Julien, Sophie Leboucher, Laetitia Besse, Patricia Legoix, Florent Dingli, Stephane Liva, Damarys Loew, Elisa Giani, Valentino Ribecco, Charita Furumaya, Laura Marcos-Kovandzic, Konstantin Masliantsev, Thomas Daubon, Lin Wang, Aaron A. Diaz, Oliver Schnell, Jürgen Beck, Nicolas Servant, Lucie Karayan-Tapon, Florence M. G. Cavalli, Giorgio Seano |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-27 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-47985-z |
| Popis: |
Abstract Glioblastoma (GBM) is a highly lethal type of cancer. GBM recurrence following chemoradiation is typically attributed to the regrowth of invasive and resistant cells. Therefore, there is a pressing need to gain a deeper understanding of the mechanisms underlying GBM resistance to chemoradiation and its ability to infiltrate. Using a combination of transcriptomic, proteomic, and phosphoproteomic analyses, longitudinal imaging, organotypic cultures, functional assays, animal studies, and clinical data analyses, we demonstrate that chemoradiation and brain vasculature induce cell transition to a functional state named VC-Resist (vessel co-opting and resistant cell state). This cell state is midway along the transcriptomic axis between proneural and mesenchymal GBM cells and is closer to the AC/MES1-like state. VC-Resist GBM cells are highly vessel co-opting, allowing significant infiltration into the surrounding brain tissue and homing to the perivascular niche, which in turn induces even more VC-Resist transition. The molecular and functional characteristics of this FGFR1-YAP1-dependent GBM cell state, including resistance to DNA damage, enrichment in the G2M phase, and induction of senescence/stemness pathways, contribute to its enhanced resistance to chemoradiation. These findings demonstrate how vessel co-option, perivascular niche, and GBM cell plasticity jointly drive resistance to therapy during GBM recurrence. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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