Microglia and glioblastoma heterocellular interplay sustains tumour growth and proliferation as an off-target effect of radiotherapy
Received date: 03 Aug 2023
Revised date: 07 Nov 2023
Accepted date: 25 Jan 2024
Copyright
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.
Cristiana Alberghina , Filippo Torrisi , Simona D'Aprile , Lucia Longhitano , Sebastiano Giallongo , Grazia Scandura , Giuliana Mannino , Stefania Mele , Maria Gabriella Sabini , Francesco P. Cammarata , Giorgio Russo , Ali S. Abdelhameed , Agata Zappalà , Debora Lo Furno , Rosario Giuffrida , Giovanni Li Volti , Daniele Tibullo , Nunzio Vicario , Rosalba Parenti . Microglia and glioblastoma heterocellular interplay sustains tumour growth and proliferation as an off-target effect of radiotherapy[J]. Cell Proliferation, 2024 , 57(6) : e13606 . DOI: 10.1111/cpr.13606
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