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• W2899681941 abstract "// Steven Georges 1, 2, * , Lidia Rodriguez Calleja 1, 2, * , Camille Jacques 1, 2, * , Melanie Lavaud 1, 2 , Brice Moukengue 1, 2 , Fernando Lecanda 3 , Thibaut Quillard 1, 2 , Marta Tellez Gabriel 1, 6 , Pierre-François Cartron 4, 5, 6, 7 , Marc Baud’huin 1, 2 , François Lamoureux 1, 2 , Dominique Heymann 4, 6 and Benjamin Ory 1, 2, 7 1 INSERM, UMR-S 1238, Nantes 44035, France 2 PhyOs, Sarcomes Osseux et Remodelage des Tissus Calcifiés, Université de Nantes, Nantes 44035, France 3 Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medic al Research, University of Navarra, Pamplona, Navarra 31008, Spain 4 Equipe Apoptose et Progression Tumorale, Centre de Recherche en Cancérologie et Immunologie Nantes Angers, CRCINA, INSERM, U1232, Université de Nantes, Université d'Angers, Nantes 44035, France 5 LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain 44800, France 6 European Associated Laboratory Sarcoma Research Unit, INSERM, University of Sheffield, Sheffield S10 2TN, UK 7 Cancéropole Grand-Ouest, Réseau Epigénétique (RepiCGO), France * These authors contributed equally to this work Correspondence to: Benjamin Ory, email: Benjamin.ory@univ-nantes.fr Keywords: osteosarcoma; microRNAs; metastasis; C-Met Received: March 09, 2018      Accepted: October 23, 2018      Published: November 06, 2018 ABSTRACT The metastatic dissemination is a complex multistep process by which tumor cells from a primary site enter into the systemic circulation to finally spread at distant sites. Even if this mechanism is rare at the tumor level, it remains the major cause of Osteosarcoma-patients’ relapse and mortality. MicroRNAs (miRNAs) have recently been described as novel epigenetics’ genes’ expression regulators actively implicated in cancer progression and dissemination. The understanding of their implication in the metastatic spreading could help clinicians to improve the outcome of osteosarcoma. We established the miRNA’s expression-profile between primary bone-tumors (PTs), circulating tumor cells (CTCs) and lung metastatic (META) samples from in vivo mice xenograft models. Our results show that the expression level of the miR-198 and -206 was decreased in META samples, in which the expression of the metastasis-related receptor C-Met was up-regulated. Those expression variations were validated in osteosarcoma patient biopsies from matching primary tumors and lung metastasis. We validated in vitro the endogenous miRNAs inhibitory effects on both migration and invasion, as well as we confirmed by luciferase assays that the C-Met receptor is one of their bona-fide targets. The anti-metastatic effect of these miRNAs was also validated in vivo , as their direct injections into the tumors reduce the number of lung-metastases and prolongs the overall survival of the treated animals. All together, our results suggest the absence of the miR-198 and -206 as powerful predictive biomarkers of the tumor cell dissemination and the rationale of their potential therapeutic use in the treatment of Osteosarcoma." @default.
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• W2899681941 date "2018-11-06" @default.
• W2899681941 modified "2023-10-11" @default.
• W2899681941 title "Loss of miR-198 and -206 during primary tumor progression enables metastatic dissemination in human osteosarcoma" @default.
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• W2899681941 doi "https://doi.org/10.18632/oncotarget.26284" @default.
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