Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

作     者：Augustin Le Naour Melissa Prat Benolt Thibault Renaud Mével Léa Lemaitre Helene Leray Marie-Veronique Joubert Kimberley Coulson Muriel Golzio Lise Lefevre Eliane Mery Alejandra Martinez Gwénael Ferron Jean-Pierre Delord Agnès Coste Bettina Couderc Augustin Le Naour;Mélissa Prat;Beno(i)t Thibault;Renaud Mével;Léa Lemaitre;Hélène Leray;Marie-Véronique Joubert;Kimberley Coulson;Muriel Golzio;Lise Lefevre;Eliane Mery;Alejandra Martinez;Gwéna(e)l Ferron;Jean-Pierre Delord;Agnès Coste;Bettina Couderc

作者机构：Institut Claudius Regaud-IUCT OncopoleUniversite de ToulouseToulouseFrance INSERM UMR 1037Cancer Research Center of Toulouse(CRCT)ToulouseFrance UMR 152 Pharma DevUniversite de ToulouseIRDUPSToulouseFrance UMR CNRS 5089Institut de Pharmacologie et de Biologie Structurale(IPBS)ToulouseFrance 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2020年第12卷第3期

页      面：202-215页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：funded by a grant from the French government(IDEX 2012)and the Groupe de recherche de l'Institut Claudius Regaud(GRICR).We are grateful to the associations‘Phil-Anthrope’and the Rotary club of Lectoure who provided a special grant for this project 

主　　题：chemoresistance macrophages mesenchymal stromal cells ovarian adenocarcinoma chemokines 

摘      要：Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells(CA-MSCs)are involved in tumor progression and *** this study,we characterize the mechanisms by which naYve mesenchymal stromal cells(MSCs)can acquire a CA-MSCs *** tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells,resulting in the secretion of high levels of CXC chemokine receptors 1 and 2(CXCR1/2)ligands such as chemokine(C-X-C motif)ligand 1(CXCL1),CXCL2,and interleukin 8(IL-8).CXCR1/2 ligands can also inhibit the immune response against ovarian tumor ***,through their released factors,CA-MSCs promote the differentiation of monocytes towards M2 macrophages,which favors tumor *** CXCR1/2 receptors are inhibited,these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral *** ex vivo and in vivo,we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of *** high concentrations of CXCR1/2 ligands in patients*blood are associated with chemoresistance,CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.