Remote neuronal activity drives glioma infiltration via Sema4f.

Autor: Huang-Hobbs E; The Integrative Molecular and Biomedical Sciences Graduate Program (IMBS), Baylor College of Medicine, Houston TX 77030.; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030., Cheng YT; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Developmental Biology, Baylor College of Medicine, Houston TX 77030., Ko Y; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX 77030.; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030., Luna-Figueroa E; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030., Lozzi B; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030.; Program in Genetics and Genomics, Baylor College of Medicine, Houston TX 77030., Taylor KR; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA., McDonald M; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Development, Disease, Models and Therapeutics, Baylor College of Medicine, Houston TX 77030., He P; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Cancer Cell Biology, Baylor College of Medicine, Houston TX 77030., Chen HC; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Cancer Cell Biology, Baylor College of Medicine, Houston TX 77030., Yang Y; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030., Maleki E; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030., Lee ZF; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Development, Disease, Models and Therapeutics, Baylor College of Medicine, Houston TX 77030., Murali S; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Cancer Cell Biology, Baylor College of Medicine, Houston TX 77030., Williamson M; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030., Choi D; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030., Curry R; The Integrative Molecular and Biomedical Sciences Graduate Program (IMBS), Baylor College of Medicine, Houston TX 77030.; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030., Bayley J; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030., Woo J; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030., Jalali A; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030., Monje M; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.; Department of Neurosurgery, Stanford University, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA., Noebels JL; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, 77030.; Department of Neurology, Baylor College of Medicine, Houston, TX 77030., Harmanci AS; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030., Rao G; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030., Deneen B; The Integrative Molecular and Biomedical Sciences Graduate Program (IMBS), Baylor College of Medicine, Houston TX 77030.; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston TX 77030.; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030.; Program in Developmental Biology, Baylor College of Medicine, Houston TX 77030.; Department of Neurosurgery, Baylor College of Medicine, Houston TX 77030.; Program in Development, Disease, Models and Therapeutics, Baylor College of Medicine, Houston TX 77030.; Program in Cancer Cell Biology, Baylor College of Medicine, Houston TX 77030.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 16. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1101/2023.03.15.532832
Abstrakt: The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity dependent infiltrating population present at the leading edge of mouse and human tumors that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified Sema4F as a key regulator of tumorigenesis and activity-dependent infiltration. Furthermore, Sema4F promotes the activity-dependent infiltrating population and propagates bi-directional signaling with neurons by remodeling tumor adjacent synapses towards brain network hyperactivity. Collectively, our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, while revealing new mechanisms of tumor infiltration that are regulated by neuronal activity.
Databáze: MEDLINE
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