Frédéric Mouriaux1, Karine Zaniolo2, Marjorie-Allison Bergeron2, Cindy Weidmann2, Arnaud De La Fouchardière3, Frédéric Fournier4, Arnaud Droit4, Mohib W Morcos5, Solange Landreville6, Sylvain L Guérin6. 1. Centre universitaire d'ophtalmologie-Recherche (CUO-Recherche), Axe médecine régénératrice, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada 2Département d'ophtalmologie, Faculté de Médecine, Université Laval, Québec, Canada 3CNRS, UMR 6301 ISTCT, CERVOxy. GIP CYCERON, Caen, France 4CHU de Rennes, Service d'Ophtalmologie, France. 2. Centre universitaire d'ophtalmologie-Recherche (CUO-Recherche), Axe médecine régénératrice, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada 5Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, Canada. 3. Département de biopathologie, Centre Léon Bérard, Lyon, France. 4. Département de médecine moléculaire, CHUL, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada. 5. Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, Canada 8Service de pathologie, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada. 6. Centre universitaire d'ophtalmologie-Recherche (CUO-Recherche), Axe médecine régénératrice, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada 2Département d'ophtalmologie, Faculté de Médecine, Université Laval, Québec, Canada 5Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, Canada.
Abstract
PURPOSE: Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). A few cell lines cultured from primary UM tumors have been used widely to investigate the pathobiology of UM. However, the translation of basic knowledge to the clinic for the treatment of the metastatic disease has remained incremental at best. In this study, we examined whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors. METHODS: Gene expression profiling by microarray was performed on UM primary tumors and derived cell lines cultured at varying passages. Expression of UM protein markers was monitored by immunohistochemical analyses and Western blotting. The in vivo tumorigenic properties of UM cultures were evaluated using athymic nude mice. RESULTS: Cell passaging severely reduced the expression of genes encoding markers typical of UM, including those of the prognostic gene signature. Marked differences between gene expression profiles of primary tumors and cell lines could be linked to the infiltrating immune and stromal cells in situ. In addition, the tumorigenic properties of UM cell lines also increased with cell passaging in culture as evaluated by their subcutaneous injection into athymic mice. CONCLUSIONS: Together, these findings demonstrate that the short-term UM primary cultures exhibit molecular features that resemble the respective surgical material and, thus, represent the best model for in vitro-assessed cancer treatments.
PURPOSE: Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). A few cell lines cultured from primary UM tumors have been used widely to investigate the pathobiology of UM. However, the translation of basic knowledge to the clinic for the treatment of the metastatic disease has remained incremental at best. In this study, we examined whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors. METHODS: Gene expression profiling by microarray was performed on UM primary tumors and derived cell lines cultured at varying passages. Expression of UM protein markers was monitored by immunohistochemical analyses and Western blotting. The in vivo tumorigenic properties of UM cultures were evaluated using athymic nude mice. RESULTS: Cell passaging severely reduced the expression of genes encoding markers typical of UM, including those of the prognostic gene signature. Marked differences between gene expression profiles of primary tumors and cell lines could be linked to the infiltrating immune and stromal cells in situ. In addition, the tumorigenic properties of UM cell lines also increased with cell passaging in culture as evaluated by their subcutaneous injection into athymic mice. CONCLUSIONS: Together, these findings demonstrate that the short-term UM primary cultures exhibit molecular features that resemble the respective surgical material and, thus, represent the best model for in vitro-assessed cancer treatments.
Authors: Lia Walcher; Clara Budde; Arina Böhm; Peter S Reinach; Priyavathi Dhandapani; Nina Ljubojevic; Markus W Schweiger; Henriette von der Waydbrink; Ilka Reimers; Josef Köhrle; Stefan Mergler Journal: Front Pharmacol Date: 2018-11-13 Impact factor: 5.810