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Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling.
- Source :
-
Cancer cell [Cancer Cell] 2023 Aug 14; Vol. 41 (8), pp. 1480-1497.e9. Date of Electronic Publication: 2023 Jul 13. - Publication Year :
- 2023
-
Abstract
- Radiation therapy (RT) provides therapeutic benefits for patients with glioblastoma (GBM), but inevitably induces poorly understood global changes in GBM and its microenvironment (TME) that promote radio-resistance and recurrence. Through a cell surface marker screen, we identified that CD142 (tissue factor or F3) is robustly induced in the senescence-associated β-galactosidase (SA-βGal)-positive GBM cells after irradiation. F3 promotes clonal expansion of irradiated SA-βGal <superscript>+</superscript> GBM cells and orchestrates oncogenic TME remodeling by activating both tumor-autonomous signaling and extrinsic coagulation pathways. Intratumoral F3 signaling induces a mesenchymal-like cell state transition and elevated chemokine secretion. Simultaneously, F3-mediated focal hypercoagulation states lead to activation of tumor-associated macrophages (TAMs) and extracellular matrix (ECM) remodeling. A newly developed F3-targeting agent potently inhibits the aforementioned oncogenic events and impedes tumor relapse in vivo. These findings support F3 as a critical regulator for therapeutic resistance and oncogenic senescence in GBM, opening potential therapeutic avenues.<br />Competing Interests: Declaration of interests H-M.J. and J.L. are co-inventors on a filed patent application for the use of truncated F7 recombinant protein to treat cancer.<br /> (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 41
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 37451272
- Full Text :
- https://doi.org/10.1016/j.ccell.2023.06.007