Abstract 1155: Chemoresistance acquisition by ovarian adenocarcinoma cells due to microenvironment

Abstract

Abstract Epithelial Ovarian Carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. We recently showed that Carcinoma-Associated-Mesenchymal Stem Cells (CA-MSC) are involved in ovarian tumor growth via the facilitation of angiogenesis in the tumor site as well as in ovarian cancer chemoresistance acquisition. Our aim is to identify the mechanisms by which CA-MSC activate tumor cells signaling pathway for both effects. First we showed that factors released by CA-MSC are able to induce angiogenic cytokines (IL-6, IL-8 and VEGF) synthesis by tumor cells in a cell line specific way. Second, CA-MSC are able to attract and activate macrophages into a M2 TAM like phenotype and allow them to secrete a huge quantity of pro-angiogenic cytokines, favorable to tumor progression of all the associated ovarian adenocarcinoma cells tested. Third, factors released by CA-MSC protect adenocarcinoma cells from carboplatin-induced apoptosis by inhibiting the activation of effector caspases 3 and 7, inducing the activation of PI3K/Akt pathway signalling and the phosphorylation of the downstream target XIAP (caspase inhibitor from IAP family). XIAP depletion by siRNA strategy or inhibitors permitted to restore carboplatin-induced apoptosis in ovarian cancer cells stimulated by CA-MSC conditioned medium . Our results suggested targeting factors released by CA-MSC could be of interest in ovarian cancer therapy. Note: This abstract was not presented at the meeting. Citation Format: Benoit Thibault, Magali Castells, Delphine Mihas, Ludivine Genre, Cecile Gandy, Eliane Mery, Jean Pierre Delord, Bettina C. Couderc. Chemoresistance acquisition by ovarian adenocarcinoma cells due to microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1155. doi:10.1158/1538-7445.AM2014-1155