Team Hugues DUFFAU – Jean-Philippe HUGNOT
Brain plasticity, stem cells and diffuse low-grade gliomas
Project Effects of intercellular mitochondria transfers from the tumor microenvironment on glioblastoma progression
PRINCIPAL INVESTIGATOR
IGF staff involved
Khattar Elias KHATTAR
PhD student, UM
Janice SAFI
PhD student, UM
The research project of the group focuses on the interactions taking place between glioblastoma cells and cells of the tumor niche and their effects on tumor progression. The team has shown that mesenchymal stem cells and astrocytes can transfer mitochondria to glioblastoma stem cells through membrane structures called tunneling nanotubes. Using the patented protocol of Mitoception, which allows the quantitative transfer of pre-isolated mitochondria to target cells, the group has shown that the acquisition of mitochondria from the tumor environment rewires the metabolism of the glioblastoma stem cells and promotes their resistance to the chemotherapeutic agent Temozolomide.
The group is currently exploiting isotope profiling approaches and investigating the mechanisms responsible for chemotherapy resistance induced by the mitochondria transferred from the tumor microenvironment. It has also developed a glioblastoma stem cell organoid model to mimic the 3D context of the tumor. This model has made it possible to highlight the changes that occur in the structure of the extracellular matrix following the acquisition of mitochondria by glioblastoma cells. The effects of these changes on the infiltration capacity of glioblastomas are currently under investigation.
Transfer of mitochondria between tumor cells and mesenchymal stem cells (MSC) through nanotubes
Main publications
• Nakhle J., et al. (2023) Cancer Res Commun, 3, 1041-56.
• Vignais M.-L., et al. (2023) Cells, 12, 582.
• Akhter W., et al. (2023) Stem Cell Research & Therapy, 14, 12.
• Khattar K., et al. (2022) Cancers 14, 1207.
• Nakhle J., et al. (2020) BioTechniques 10.2144/btn-2020-0114.
• Nakhle J., et al. (2020) Int. J. Mol. Sci. 21, 4405
• Hekmatshoar Y., et al. (2018) Biochemical Journal 475, 2305-2328.
• Caicedo, A., et al. (2015) Sci. Rep., 5, 9073.
Funding
• 2021-2025 ANR MiMeTic – Partner
• 2021-2024 La Ligue – PhD PI
• 2022-2023 Region Occitanie Prematuration contract – Principal investigator
• 2021-2022 GSO Emergence – Principal investigator
• 2020-2021 ARC – Principal investigator
Collaborations
• Anne-Marie Rodriguez, Paris
• Nicolas Buisine, Paris
• Floriant Bellvert, Toulouse
• Thierry Virolle, Nice
• Lucille Stuani, IRCM, Montpellier
• Tristan Bouschet, IGF, Montpellier
Alumni
• Nakhle Jean (PhD, 2017-2020)
• Caicedo Andrès (PhD, 2011-2014)
Patents
• Vignais, M.-L., Brondello J.-M., Jorgensen, C. Caicedo, A. WO 2016008937-A1 (2015)
