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VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance.
Pichol-Thievend, Cathy; Anezo, Oceane; Pettiwala, Aafrin M; Bourmeau, Guillaume; Montagne, Remi; Lyne, Anne-Marie; Guichet, Pierre-Olivier; Deshors, Pauline; Ballestín, Alberto; Blanchard, Benjamin; Reveilles, Juliette; Ravi, Vidhya M; Joseph, Kevin; Heiland, Dieter H; Julien, Boris; Leboucher, Sophie; Besse, Laetitia; Legoix, Patricia; Dingli, Florent; Liva, Stephane; Loew, Damarys; Giani, Elisa; Ribecco, Valentino; Furumaya, Charita; Marcos-Kovandzic, Laura; Masliantsev, Konstantin; Daubon, Thomas; Wang, Lin; Diaz, Aaron A; Schnell, Oliver; Beck, Jürgen; Servant, Nicolas; Karayan-Tapon, Lucie; Cavalli, Florence M G; Seano, Giorgio.
Afiliação
  • 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.
  • Bourmeau G; Institut Curie, PSL University, 75005, Paris, France.
  • Montagne R; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Lyne AM; Institut Curie, PSL University, 75005, Paris, France.
  • Guichet PO; INSERM U900, 75005, Paris, France.
  • Deshors P; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France.
  • Ballestín A; Institut Curie, PSL University, 75005, Paris, France.
  • Blanchard B; INSERM U900, 75005, Paris, France.
  • Reveilles J; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France.
  • Ravi VM; Université de Poitiers, CHU Poitiers, ProDiCeT, F-86000, Poitiers, France.
  • Joseph K; CHU Poitiers, Laboratoire de Cancérologie Biologique, F-86000, Poitiers, France.
  • Heiland DH; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Julien B; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Leboucher S; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Besse L; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Legoix P; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Dingli F; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Liva S; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Loew D; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Giani E; Histology Facility, Institut Curie, 91400, Orsay, France.
  • Ribecco V; Institut Curie, PSL University, Université Paris-Saclay, CNRS UMS2016, INSERM US43, Multimodal Imaging Center, 91400, Orsay, France.
  • Furumaya C; Institut Curie, PSL University, ICGex Next-Generation Sequencing Platform, 75005, Paris, France.
  • Marcos-Kovandzic L; Institut Curie, PSL University, CurieCoreTech Spectrométrie de Masse Protéomique, 75005, Paris, France.
  • Masliantsev K; Institut Curie, PSL University, 75005, Paris, France.
  • Daubon T; INSERM U900, 75005, Paris, France.
  • Wang L; MINES ParisTeach, CBIO-Centre for Computational Biology, PSL Research University, 75006, Paris, France.
  • Diaz AA; Institut Curie, PSL University, CurieCoreTech Spectrométrie de Masse Protéomique, 75005, Paris, France.
  • Schnell O; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Italy.
  • Beck J; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Servant N; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Karayan-Tapon L; Institut Curie, INSERM U1021, CNRS UMR3347, Tumor Microenvironment Lab, Paris-Saclay University, 91400, Orsay, France.
  • Cavalli FMG; Université de Poitiers, CHU Poitiers, ProDiCeT, F-86000, Poitiers, France.
  • Seano G; CHU Poitiers, Laboratoire de Cancérologie Biologique, F-86000, Poitiers, France.
Nat Commun ; 15(1): 3602, 2024 Apr 29.
Article em En | MEDLINE | ID: mdl-38684700
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article