VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance.

Autor: Pichol-Thievend C; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Anezo O; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Pettiwala AM; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.; Institut Curie, PSL University, 75005, Paris, France., Bourmeau G; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Montagne R; Institut Curie, PSL University, 75005, Paris, France.; INSERM U900, 75005, Paris, France.; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France., Lyne AM; Institut Curie, PSL University, 75005, Paris, France.; INSERM U900, 75005, Paris, France.; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France., Guichet PO; Université de Poitiers, CHU Poitiers, ProDiCeT, F-86000, Poitiers, France.; CHU Poitiers, Laboratoire de Cancérologie Biologique, F-86000, Poitiers, France., Deshors P; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Ballestín A; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Blanchard B; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Reveilles J; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Ravi VM; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany., Joseph K; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany., Heiland DH; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany., Julien B; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Leboucher S; Histology Facility, Institut Curie, 91400, Orsay, France., Besse L; Institut Curie, PSL University, Université Paris-Saclay, CNRS UMS2016, INSERM US43, Multimodal Imaging Center, 91400, Orsay, France., Legoix P; Institut Curie, PSL University, ICGex Next-Generation Sequencing Platform, 75005, Paris, France., Dingli F; Institut Curie, PSL University, CurieCoreTech Spectrométrie de Masse Protéomique, 75005, Paris, France., Liva S; Institut Curie, PSL University, 75005, Paris, France.; INSERM U900, 75005, Paris, France.; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France., Loew D; Institut Curie, PSL University, CurieCoreTech Spectrométrie de Masse Protéomique, 75005, Paris, France., Giani E; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Italy., Ribecco V; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Furumaya C; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Marcos-Kovandzic L; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France., Masliantsev K; Université de Poitiers, CHU Poitiers, ProDiCeT, F-86000, Poitiers, France.; CHU Poitiers, Laboratoire de Cancérologie Biologique, F-86000, Poitiers, France., Daubon T; Université Bordeaux, CNRS, IBGC, UMR5095, Bordeaux, France., Wang L; Department of Computational and Quantitative Medicine, Hematologic Malignancies Research Institute and Beckman Research Institute, City of Hope, Duarte, CA, USA., Diaz AA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Schnell O; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany., Beck J; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany., Servant N; Institut Curie, PSL University, 75005, Paris, France.; INSERM U900, 75005, Paris, France.; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France., Karayan-Tapon L; Université de Poitiers, CHU Poitiers, ProDiCeT, F-86000, Poitiers, France.; CHU Poitiers, Laboratoire de Cancérologie Biologique, F-86000, Poitiers, France., Cavalli FMG; Institut Curie, PSL University, 75005, Paris, France.; INSERM U900, 75005, Paris, France.; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France., Seano G; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France. giorgio.seano@curie.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 29; Vol. 15 (1), pp. 3602. Date of Electronic Publication: 2024 Apr 29.
DOI: 10.1038/s41467-024-47985-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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