Implication de la phostine 3.1a sur l’angiogenèse, le métabolisme endothélial et les pathologies associées

Abstract : Actual anti-angiogenic therapies are limited, and targeting endothelial metabolism is a new promising strategy. One of the lead compound of the Phostin family, PST 3.1a has anti-glioblastoma properties both in vitro and in vivo. The objective of the present study was to assess the effect of PST3.1a on angiogenesis and endothelial metabolism. Angiogenesis is a complex process describing the growth of new blood vessels from existing vasculature, triggered by local pro-angiogenic factors such as the vascular endothelial growth factor (VEGF). Angiogenesis takes part in various pathological conditions and particularly in tumor growth. PST 3.1a (10 μM) inhibited the main steps leading to angiogenesis in vitro including migration, proliferation, adhesion and tube formation. PST 3.1a also reduced physiological angiogenesis in both mice and zebrafish models, and pathological angiogenesis and glioblastoma progression in vivo. In addition, our results highlight the alteration of the interaction between VEGF receptor 2 and galectin-1, a binding known as a key component of the regulation of angiogenesis associated to tumor resistance.These results provide a new route towards an innovative and original approach to target angiogenesis related diseases, including cancer.
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Simon Bousseau. Implication de la phostine 3.1a sur l’angiogenèse, le métabolisme endothélial et les pathologies associées. Médecine humaine et pathologie. Université d'Angers, 2018. Français. ⟨NNT : 2018ANGE0029⟩. ⟨tel-02137407⟩

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