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Etude de l’impact de la vitronectine et de la fibronectine ascitiques sur la récidive des carcinomes ovariens

Abstract : Ovarian cancers are the leading cause of death among gynaecological cancers in western countries. Most of these cancers are diagnosed at a late stage, when ovarian cancer cells have spread and colonized the walls of the abdominal cavity. Therefore, these cancers are associated to a poor prognosis.More than one third of the patients show an accumulation of ascites at the time of the diagnosis. Ascites are exudative fluids composed of a cellular and also an acellular fraction. In fact, ascites constitute a dynamic reservoir of bioactive molecules. Even if the response of ovarian cancers to the current first-line therapy, that consit in debulking surgery followed by chemotherapy, is satisfactory, the rate of recurrence remains important. The gain of a chemoresistance and the atypical widespread of cancer cells are two important factors involved in the recurence of the ovarian cancers.The role of ascites and more particularly, of the ascitic matrix componants on the dissemination process and on the chemoresitance of the ovarian cancer cells remain poorly studied and is the aim of this work.The objective of this study was to investiguate the influence of ascites and of two matrix glycoproteins purified from samples of ascites i) on the cells behavior convenient to the dissemination and the recurrence of the ovarian cancers and ii) on the response of cells to therapeutics treatments with platinum.This study suggests that ascites are a permissive microenvironment to the dissemination of ovarian cancer cells and that ascitic fibronectin and vitronectin as well as their specific receptors are actors which participate to the regulation of this dissemination. Ascites also protect ovarian cancer cells against the cytotoxicity of chemotherapeutic drugs.These results illustrate the potential interest of ascites derived fibronectin and vitronectin as diagnosis tools and/or therapeutic targets for ovarian cancers and encourage us to deepen the study of these two molecules and their consequences in the progress of the disease.
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https://tel.archives-ouvertes.fr/tel-01409759
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Submitted on : Tuesday, December 6, 2016 - 11:16:13 AM
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Lyvia Blay. Etude de l’impact de la vitronectine et de la fibronectine ascitiques sur la récidive des carcinomes ovariens. Biologie cellulaire. Université de Cergy Pontoise, 2016. Français. ⟨NNT : 2016CERG0811⟩. ⟨tel-01409759⟩

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