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Les thérapies ciblées anti-EGFR ont-elles un réel effet anti-angiogénique ? Etude in vitro de l'angiogenèse induite par des cellules cancéreuses des VADS traitées ou non par le Cetuximab

Abstract : Overexpression of EGFR has a major role in the development of head and neck squamous cell carcinoma (HNSCC) and its inhibition by anti-EGFR antibodies (cetuximab) induced an anti-tumor effect but could also induce an anti-angiogenic effect. However, the effects of these agents onto angiogenesis and endothelial cells (EC) have not really been evaluated. The objective of this work is to study angiogenesis induced by mediators released by head and neck squamous carcinoma cells (Cal27, FaDu) in culture media with or without cetuximab exposure, known as conditioned media (CM). Cetuximab has no significant direct effect on EC. It induces a decrease in the secretion of VEGF by tumor cells but, paradoxically, the CM induces a pro-angiogenic effect. The analysis of the composition of the CM does not allow us to identify a key molecule responsible for this effect because cetuximab decreases the secretion of both pro- and anti-angiogenic factors by tumor cells. To explain this paradox and in agreement with the literature, we highlighted the release of microvesicles by our tumor cells (TMV), TMV which express EGFR and TF, and regulation of this release and the content of TMV after cetuximab exposure. These TMV may interact with the EC and cetuximab increases this interaction. Further characterization of TMV and studying their role in the angiogenic process in response to cetuximab will allow us in the future to understand the real activity of anti-EGFR antibodies onto angiogenesis
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https://hal.univ-lorraine.fr/tel-01746264
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Valérie Jouan-Hureaux. Les thérapies ciblées anti-EGFR ont-elles un réel effet anti-angiogénique ? Etude in vitro de l'angiogenèse induite par des cellules cancéreuses des VADS traitées ou non par le Cetuximab. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10115⟩. ⟨tel-01746264⟩

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