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Influence du stroma et des cellules souches mésenchymateuses sur la dissémination et la résistance au traitement des carcinomes ovariens épithéliaux

Abstract : Patients with epithelial ovarian cancer (EOC) are diagnosed with advanced stage in 75% of cases and most of them will relapse despite a good primary response to chemotherapy, thus explaining the bad prognosis of EOC. While tumor microenvironment seems to play an important role for the development and survival of cancer cells, there is only few data regarding the mesenchymal stem cells (MSC) in EOC. In this work we therefore aimed at identifying the molecular determinant between MSC and ovarian cancer cells. In the first part of this work, we demonstrated that ovarian cancer cells acquired pro-metastatic profile upon contact with MSC. We then showed that MSC could enhance ovarian cancer cells infiltration through IL6 secretion in an amniochorionic membrane based 3D model. Finally we showed that MSC could protect ovarian cancer cells from hyperthermia through CXCL12 secretion. Taken together, our data are concordant to reveal the pro-tumoral properties of MSC. Cytokine inhibitors interrupting the cross-talk between OCC and MSC should now be tested as new therapies for EOC.
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Cyril Touboul. Influence du stroma et des cellules souches mésenchymateuses sur la dissémination et la résistance au traitement des carcinomes ovariens épithéliaux. Biologie cellulaire. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA11T072⟩. ⟨tel-00907889⟩

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