ORIGINAL ARTICLESCharacterization of the typical multidrug resistance profile in human uveal melanoma cell lines and in mouse liver metastasis derivativesLabialle, Stéphanea; Dayan, Guilab; Gambrelle, Joëlb c; Gayet, Landryb; Barakat, Stéphaneb; Devouassoux-Shisheboran, Mojgand; Bernaud, Jeaninee; Rigal, Dominiquee; Grange, Jean-Danielc; Baggetto, Loris G.bAuthor Information aMcGill University, Royal Victoria Hospital, F3.32, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada bInstitut de Biologie et Chimie des Protéines (IBCP UMR5086 CNRS UCBL), 7 Passage du Vercors, F-69367 Lyon Cedex 07, France cService d'Ophthalmologie, Hôpital de la Croix-Rousse, 103 Gde rue de la Croix-Rousse, F-69317 Lyon Cedex 04, France dLaboratoire d'Anatomie et de Cytologie Pathologiques, Hôpital de la Croix-Rousse, 103 Gde rue de la Croix-Rousse, F-69317 Lyon Cedex 04, France eEtablissement Français du Sang, 1 Passage du Vercors, F-69007 Lyon, France Sponsorship: This work was supported by grants from the Association Rétina France, Ligue Contre le Cancer (Comité du Rhône, Comité de la Loire, Comité National), Association pour la Recherche sur le Cancer (ARC), Fondation Mérieux, Fondation pour la Recherche Médicale and Centre National de la Recherche Scientifique (CNRS). Correspondence and requests for reprints to Dr Loris G. Baggetto, IBCP UMR5086 CNRS UCBL, 7 Passage du Vercors, F-69367 Lyon Cedex 07, France Tel: +33 (0)4 72 72 26 35; fax: +33 (0)4 72 72 26 26; e-mail: [email protected] Received 16 April 2004 Accepted (after revision) 30 December 2004 Melanoma Research: August 2005 - Volume 15 - Issue 4 - p 257-266 Buy Abstract Uveal melanoma is the most common intraocular malignancy. To study its biology, stable cell lines provide a useful tool, but these are very difficult to obtain. A stable and rapidly growing human choroidal melanoma cell line composed of pure epithelioid cells was established and maintained for at least 4 years. In vivo transplantation into BALB/cByJ nude mice induced vascularized tumours at the injection sites. Interestingly, two of three cases produced a liver metastasis. Other uveal melanoma cell lines displaying different morphological aspects were also obtained. To avoid the bias due to uncertain immunologically based staining approaches, several methods were juxtaposed to establish the multidrug resistance (MDR) profile. All the uveal melanomas studied expressed significant levels of the MDR-related MDR1, MRP1 (MDR-related protein 1) and LRP/MVP (lung resistance protein/major vault protein) messenger RNAs (mRNAs), produced their corresponding proteins and were able to functionally extrude daunomycin. When compared with the established MEWO skin melanoma cell line, our data showed that both primary and metastatic uveal melanomas intrinsically expressed the typical MDR phenotype, which precludes the use of any anticancer drugs known to be substrates of MDR-related proteins to treat the disease. Moreover, it appears that the metastasizing process does not change the status of the MDR phenotype. © 2005 Lippincott Williams & Wilkins, Inc.