Role of metabolism in radiation-induced plasticity and heterogeneity of Glioma stem cells
This translational research team, in the context of its work on the radiosensitisation of glioblastomas, has set up a new research axis on the involvement of glioblastoma stem cells in the radioresistance of these tumours. In 2010, this group initiated a project focusing on the plasticity of Glioblastoma cells in response to radiotherapy, a plasticity that could explain their radioresistance and the systematic presence of recurrence, even after surgical resection and radio-chemotherapy. He was able to demonstrate that ionising radiation causes phenotypic and metabolic plasticity in patients’ Glioblastoma cells, as well as the acquisition of cancer stem cell-like traits and functions, a phenomenon known as dedifferentiation (Dahan et al 2014 PMID: 25429620). The research of this group has focused on the identification of new radiosensitising targets specific to these Glioblastoma stem cells by identifying in particular integrin b8 (Malric et al 2017 & 2019, PMID: 29156849 and PMID: 30266751) and survivin (Dahan et al 2014 PMID: 25429620).
The line of research developed today focuses on the study of intra-patient tumour heterogeneity and its role in radioresistance (Boyrie et al 2018, PMID: 30333910). It has been shown by the team that metabolically active areas of the tumour defined by MRI spectroscopy in gliobalstoma patients (Laprie et al, 2008 PMID: 18262090; Deviers et al 2014 PMID: 25104068), known to be specific sites of tumour recurrence, were enriched in Glioblastoma stem cells (Lemarié et al in preparation). This project therefore focuses on this intra-tumoral heterogeneity in order to characterise the cancer stem cells from these areas and to establish their radioresistance profile, their transcriptomic profile (RNAseq), and their metabolic profile (metabolome analysis, Seahorse flow analyser), both in vitro and in vivo (MRI spectroscopy method). The objective of this project is to identify specific metabolic targets for these Glioblastoma stem cells in order to better radiosensitize these metabolically active areas in the patient and thus block tumor recurrence.
Metabolism, plasticity, dedifferentiation, Glioblastoma stem cells, tumour heterogeneity
Partners and funders
Ligue contre le Cancer (Tarn, Hautes-Pyrénées), ARTC, FRM, INCA Plan Cancer, canceropôle GSO