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Plasticité des cellules tumorales de glioblastomes : inter-conversion d’un phénotype différencié et souche en fonction du microenvironnement

Abstract : There is great interest but little understanding in how cancer stem cells arise. Here we show that tumor cells exhibiting stem-like properties and expression of stemness(CD133) and pluripotency markers (SOX2, NANOG, OCT4), can arise from differentiated tumor cells that are isolated from human glioblastomas. These cells could transit from a more differentiated state that cannot self-renew to a self-renewing stem-like state upon EGF/EGFR signaling. This dedifferentiation process induced expression of pluripotency markers, and restored clonal and tumorigenic properties as well as resistance to temozolomide, the chemotherapy of reference. EGF/EGFR signaling including ERK activation was crucial for this cellular reprogramming. Interestingly, expression of pluripotency markers occurred before the cells re-entered the cell cycle, demonstrating that the cells have the capacity to change and reprogram before the cell division starts. Our findings support a model of tumor homeostasis in which tumor cells driven by environmental cues such as EGF, can spontaneously acquire stem-like properties contributing thus to the enrichment in tumor propagating cells.
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https://tel.archives-ouvertes.fr/tel-01832315
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Submitted on : Saturday, July 7, 2018 - 1:02:33 AM
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Fabien Almairac. Plasticité des cellules tumorales de glioblastomes : inter-conversion d’un phénotype différencié et souche en fonction du microenvironnement. Sciences agricoles. Université Nice Sophia Antipolis, 2016. Français. ⟨NNT : 2016NICE4045⟩. ⟨tel-01832315⟩

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