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Microglia and glioblastoma heterocellular interplay sustains tumour growth and proliferation as an off-target effect of radiotherapy.
- Source :
-
Cell proliferation [Cell Prolif] 2024 Jun; Vol. 57 (6), pp. e13606. Date of Electronic Publication: 2024 Mar 07. - Publication Year :
- 2024
-
Abstract
- Glioblastoma (GBM), a WHO grade IV glioma, is a malignant primary brain tumour for which combination of surgery, chemotherapy and radiotherapy is the first-line approach despite adverse effects. Tumour microenvironment (TME) is characterized by an interplay of cells and soluble factors holding a critical role in neoplastic development. Significant pathophysiological changes have been found in GBM TME, such as glia activation and oxidative stress. Microglia play a crucial role in favouring GBM growth, representing target cells of immune escape mechanisms. Our study aims at analysing radiation-induced effects in modulating intercellular communication and identifying the basis of protective mechanisms in radiation-naïve GBM cells. Tumour cells were treated with conditioned media (CM) derived from 0, 2 or 15 Gy irradiated GBM cells or 0, 2 or 15 Gy irradiated human microglia. We demonstrated that irradiated microglia promote an increase of GBM cell lines proliferation through paracrine signalling. On the contrary, irradiated GBM-derived CM affect viability, triggering cell death mechanisms. In addition, we investigated whether these processes involve mitochondrial mass, fitness and oxidative phosphorylation and how GBM cells respond at these induced alterations. Our study suggests that off-target radiotherapy modulates microglia to support GBM proliferation and induce metabolic modifications.<br /> (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Humans
Cell Line, Tumor
Culture Media, Conditioned pharmacology
Cell Survival radiation effects
Mitochondria metabolism
Mitochondria radiation effects
Glioblastoma radiotherapy
Glioblastoma pathology
Glioblastoma metabolism
Microglia metabolism
Microglia pathology
Microglia radiation effects
Cell Proliferation radiation effects
Tumor Microenvironment radiation effects
Brain Neoplasms pathology
Brain Neoplasms radiotherapy
Brain Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2184
- Volume :
- 57
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell proliferation
- Publication Type :
- Academic Journal
- Accession number :
- 38454614
- Full Text :
- https://doi.org/10.1111/cpr.13606