TY - JOUR T1 - Patient-derived Glioblastoma Stem cells transfer mitochondria through Tunneling Nanotubes in Tumor Organoids JF - bioRxiv DO - 10.1101/2020.11.21.392597 SP - 2020.11.21.392597 AU - Giulia Pinto AU - Inés Saenz-de-Santa-Maria AU - Patricia Chastagner AU - Emeline Perthame AU - Caroline Delmas AU - Christine Toulas AU - Elizabeth Moyal-Jonathan-Cohen AU - Christel Brou AU - Chiara Zurzolo Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/22/2020.11.21.392597.abstract N2 - Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.Competing Interest StatementThe authors have declared no competing interest.AbbreviationGBMGlioblastomaGSCsGlioblastoma Stem CellsGSLCsGlioblastoma Stem-Like CellsTNTsTunneling NanotubeTMsTumor MicrotubeTubβ3Class III β-TubulinCHI3L3Chitinase 3-Like-3GFAPGlial Fibrillary Acidic ProteinGAP43Growth-Associated Protein 43Olig1Oligodendrocyte transcription factor 1Olig2Oligodendrocyte transcription factor 2Sox2Sex-determining-region-Y-Box Transcription Factor 2Sox11Sex-determining-region-Y-Box Transcription Factor 11TOM20Translocase of Outer MembraneOCROxygen consumption rateFCCPCarbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone ER -