AB030. Characterization of the interactions between hepatic stellate cells and tumor cells during uveal melanoma metastatic progression

作     者：Léo Piquet William Pelletier Peter Gerges Julie Bérubé Solange Landreville 

作者机构：Centre de recherche du CHU de Québec-UniversitéLavalHôpital du Saint-SacrementQuébecQCCanada Centre de recherche en organogénèse expérimentale de l’UniversitéLaval/LOEXQuébecQCCanada Département d’ophtalmologie et d’ORL-CCFFacultéde médecineUniversitéLavalQuébecQCCanada 

出 版 物：《Annals of Eye Science》 (眼科学年鉴（英文）)

年 卷 期：2018年第1期

页      面：436-436页

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

主　　题：Uveal melanoma(UM) hepatic stelllate cells-interaction metastasis 

摘      要：Background:Uveal melanoma(UM)is the most common primary eye tumor in adults,and the most frequent site of malignant transformation of the melanocytes after the *** spreads to the liver in half of the cases,and the death rate following the report of metastasis is 92%at 2 *** tropism of UM cannot simply be explained by the blood circulatory system organization,and illustrates the“seed and soilhypothesis that describes an interaction between tumor cells(seed)and a specific microenvironment(soil).We decided to focus our study on the synergic interaction between UM cells and hepatic stellate cells(HSC),whose role has been previously described in the metastatic progression of colon and pancreatic ***,HSC have been found surrounding UM liver metastasis,and the UM secretome contains activating cytokines of hepatic stromal *** hypothesis is that HSC provide a specific microenvironment in the liver enhancing the growth of UM cells and increasing their therapeutic *** an in vitro 3D model and an original xenograft mouse model,we aim to decipher the mechanisms of UM metastatic progression,in order to elaborate new therapeutic ***:First,using an agar coating,spheroids were generated with UM cells and were allowed to grow for 72 *** tumor spheroids were then embedded in Matrigel and the HSC conditioned medium was used to evaluate the impact of the HSC secretome on UM ***,an original in vivo xenograft mouse model was generated,in which metastatic UM cells were injected alone or with human HSC in the spleen of immunodeficient *** model allows us to evaluate in 3-6 weeks the metastatic potential of each cell population,and thus to determine the cooperation between HSC and UM cells in the ***:The HSC conditioned medium increased the invasion of UM spheroids compared to non-conditioned medium in our in vitro *** addition,UM cells inoculated in the mouse spleen alone or with human HSC we