Microglia and glioblastoma heterocellular interplay sustains tumour growth and proliferation as an off-target effect of radiotherapy.

Publisher: Published for the Cell Kinetics Society, the European Study Group for Cell Proliferation, and the International Cell Cycle Society by Blackwell Scientific Publications Country of Publication: England NLM ID: 9105195 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2184 (Electronic) Linking ISSN: 09607722 NLM ISO Abbreviation: Cell Prolif Subsets: MEDLINE

Original Publication: [Oxford, England] : Published for the Cell Kinetics Society, the European Study Group for Cell Proliferation, and the International Cell Cycle Society by Blackwell Scientific Publications, 1991-

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; Humans ; Cell Line, Tumor ; Culture Media, Conditioned/pharmacology ; Cell Survival/radiation effects ; Mitochondria/metabolism ; Mitochondria/radiation effects

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.
(© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

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PNC0000003 National Plan for NRRP Complementary Investments; MD-RESETT-GLIO Piano di Incentivi per la Ricerca di Ateneo 2020-2022, Linea di Intervento 2; E66C18001240007 PON AIM R&I 2014-2020; Fondazione Umberto Veronesi; PhD Program in Biotechnology (Department of Biomedical and Biotechnological Sciences, University of Catania)

0 (Culture Media, Conditioned)

Date Created: 20240308 Date Completed: 20240605 Latest Revision: 20240607

20240607

PMC11150140

10.1111/cpr.13606

38454614