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Mise en évidence des propriétés chimiotactiques de l’oxygène pour des cellules épithéliales : implication du récepteur EGFR dans l’aérotaxie

Abstract : Cell migration is a crucial process during embryonic development, wound healing, immune system but also metastasis. Success of these processes relies on the capacities of cells to sense an asymmetric signal, interpret it and orient themselves to migrate in a directed manner. In vivo, migration is guided by several signals from the cellular microenvironment. Hypoxia, or decrease in the level of tissue oxygen, is an important feature of the cellular environment in the embryo and in solid tumors. Owing to the limitation of oxygen diffusion, hypoxia often generates oxygen gradients in vivo. We have developed an original method in which epithelial cells themselves generate oxygen gradient in vitro. And interestingly, these cells are able to migrate directionally to higher oxygen concentrations. This aerotaxis ability is independent of mitochondrial respiration and hypoxia response pathway. The reactive oxygen species (ROS) would mediate the migratory response to the gradient. The asymmetric production of ROS between the front and the back of the cells would be at the origin of the differential activation of the EGFR receptor and the persistence of cells towards higher oxygen concentrations. This chemoattractant capacity of oxygen, known in bacteria, but not described for eukaryotic cells, could play a major role in embryonic development and in metastatic dissemination
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Mathieu Deygas. Mise en évidence des propriétés chimiotactiques de l’oxygène pour des cellules épithéliales : implication du récepteur EGFR dans l’aérotaxie. Biologie cellulaire. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1261⟩. ⟨tel-01879097v2⟩

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