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Glioblastoma remodelling of human neural circuits decreases survival.
Krishna, Saritha; Choudhury, Abrar; Keough, Michael B; Seo, Kyounghee; Ni, Lijun; Kakaizada, Sofia; Lee, Anthony; Aabedi, Alexander; Popova, Galina; Lipkin, Benjamin; Cao, Caroline; Nava Gonzales, Cesar; Sudharshan, Rasika; Egladyous, Andrew; Almeida, Nyle; Zhang, Yalan; Molinaro, Annette M; Venkatesh, Humsa S; Daniel, Andy G S; Shamardani, Kiarash; Hyer, Jeanette; Chang, Edward F; Findlay, Anne; Phillips, Joanna J; Nagarajan, Srikantan; Raleigh, David R; Brang, David; Monje, Michelle; Hervey-Jumper, Shawn L.
Afiliação
  • Krishna S; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Choudhury A; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Keough MB; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Seo K; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Ni L; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Kakaizada S; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Lee A; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Aabedi A; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Popova G; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Lipkin B; Department of Psychology, University of Michigan, Ann Arbor, MI, USA.
  • Cao C; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Nava Gonzales C; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Sudharshan R; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Egladyous A; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Almeida N; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Zhang Y; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Molinaro AM; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Venkatesh HS; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Daniel AGS; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Shamardani K; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Hyer J; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Chang EF; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Findlay A; Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Phillips JJ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
  • Nagarajan S; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Raleigh DR; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
  • Brang D; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
  • Monje M; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Hervey-Jumper SL; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Nature ; 617(7961): 599-607, 2023 May.
Article em En | MEDLINE | ID: mdl-37138086
ABSTRACT
Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Vias Neurais Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Vias Neurais Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos