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Rôle du récepteur des androgènes dans les communications cellulaires au sein du cancer de la prostate

Abstract : Androgen ablation therapy remains the most common treatment for patients with advanced prostate cancer. However, most patients will relapse due to the emergence of truncated constitutively active androgen receptor (AR) variants. The tumor microenvironment is another necessary feature driving prostate cancer progression. Cancer associated fibroblasts (CAFs) are the major specialized stromal cells that favor tumor progression. These cells are very heterogeneous and derive from several other cell types as mesenchymal stem cells (MSCs). In order to highlight the impact of AR variants on surrounding tumor stroma, the aim of my project was to investigate the effects of these AR variants on MSCs differentiation into CAFs. I noticed that the expression of VEGF, a CAF differentiation factor, was upregulated in tumor cells expressing AR Q641X variant. Similarly, the expression of CAF differentiation markers FSP-1, CXCL12, PDGFR-β, and VEGF was enhanced in MSCs in presence of AR Q641X variant. These data highlight an unknown property of AR Q641X variant in prostate tumor cells that is its ability to induce MSCs differentiation into CAFs, underlining the urgent need to develop novel strategies targeting these AR variants.
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Edwige Schreyer. Rôle du récepteur des androgènes dans les communications cellulaires au sein du cancer de la prostate. Biologie moléculaire. Université de Strasbourg, 2018. Français. ⟨NNT : 2018STRAJ098⟩. ⟨tel-02494698⟩

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