title: Effects of Long-term Serial Passaging on the Characteristics and Properties of Cell Lines Derived From Uveal Melanoma Primary Tumors.
abstract: OBJECTIVE
  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.affiliation: 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.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mouriaux
authors.affiliation: 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.
authors.forename: Karine
authors.initials: K
authors.lastname: Zaniolo
authors.affiliation: 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.
authors.forename: Marjorie-Allison
authors.initials: MA
authors.lastname: Bergeron
authors.affiliation: 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.
authors.forename: Cindy
authors.initials: C
authors.lastname: Weidmann
authors.affiliation: Département de biopathologie, Centre Léon Bérard, Lyon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: De La Fouchardière
authors.affiliation: Département de médecine moléculaire, CHUL, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fournier
authors.affiliation: Département de médecine moléculaire, CHUL, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Droit
authors.affiliation: 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.
authors.forename: Mohib W
authors.initials: MW
authors.lastname: Morcos
authors.affiliation: 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.
authors.forename: Solange
authors.initials: S
authors.lastname: Landreville
authors.affiliation: 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.
authors.forename: Sylvain L
authors.initials: SL
authors.lastname: Guérin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D058965:MART-1 Antigen / Q000096:biosynthesis / Q000235:genetics*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008858:Microscopy, Phase-Contrast; D009374:Neoplasms, Experimental; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D058965:MART-1 Antigen; D012334:RNA, Neoplasm