Rôle du monoxyde d'azote dans la reconnaissance cellulaire : étude d'un modèle endothélial lié au mélanome

Abstract : Melanoma is the rarest skin cancer, but one that causes the most of deaths. The critical step of itsprogression is angiogenesis, a physiological tumor-activated process which allows the delivery ofoxygen and nutrients. Tumor cells may then metastasize to the lymph nodes, in particular. Moreover,the tumor inhibits the host immune responses toward itself. All these mechanisms are regulated bynitric oxide (NO ). The aim of the project was to deepen the role of NO in angiogenesis andleukocyte recruitment, two mechanisms based on endothelial cell recognition.We have shown here that NO is necessary for angiogenesis, but that high concentrations are antiangiogenic.This inhibitory effect of NO can be attributed to the decrease of cell-cell interactions andthe inhibition of the PECAM-1/CD31 expression, mainly.Besides, we have demonstrated that leukocyte adhesion on endothelium is inhibited by NO . This canbe explained by the modulation of the expression of molecules able to bind to chemokines:glycosaminoglycans and chemokine receptors, as well as by the down-regulation of the adhesionmolecules CD34 and ICAM-2/CD102 VCAM-1/CD106.In conclusion, NO is able to regulate the main cellular mechanisms of tumor progression bymodulating the expression of surface molecules on endothelial cells. Throughout this work, we haveobserved that these modulations depend on NO concentrations and on the cell type, demonstratingthe pivotal role of NO in cancer progression.
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Life Sciences. Université d'Orléans, 2010. French. <NNT : 2010ORLE2028>


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Aude Carreau. Rôle du monoxyde d'azote dans la reconnaissance cellulaire : étude d'un modèle endothélial lié au mélanome. Life Sciences. Université d'Orléans, 2010. French. <NNT : 2010ORLE2028>. <tel-00585128>

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