title: TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models.
abstract: Ewing sarcoma (EWS) is the second most frequent pediatric malignant bone tumor. EWS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine TNF-Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, certain EWS cell lines appear resistant to recombinant human (rh) TRAIL-induced apoptosis. We therefore hypothesized that a TRAIL presentation at the surface of the carrier cells might overcome this resistance and trigger apoptosis. For this purpose, human adipose mesenchymal stromal/stem cells (MSC) transfected in a stable manner to express full-length human TRAIL were co-cultured with several human EWS cell lines, inducing apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL or AMG655, an antibody agonist to the death receptor, DR5. In vivo, TRAIL delivered by MSCs was able to counteract tumor progression in two orthotopic models of Ewing sarcoma, associated with caspase activation, indicating that a cell-based delivery of a potent apoptosis-inducing factor could be relevant in EWS.
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
authors: Romain
authors: R
authors: Guiho
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
authors: Kevin
authors: K
authors: Biteau
authors: Department of Medical and Surgical Sciences for Children and Adults, Laboratory of Cellular Therapy, University Hospital of Modena and Reggio Emilia, Modena, Italy.
authors: Giulia
authors: G
authors: Grisendi
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
authors: Julien
authors: J
authors: Taurelle
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
authors: Mathias
authors: M
authors: Chatelais
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
authors: Malika
authors: M
authors: Gantier
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
authors: Dominique
authors: D
authors: Heymann
authors: Department of Medical and Surgical Sciences for Children and Adults, Laboratory of Cellular Therapy, University Hospital of Modena and Reggio Emilia, Modena, Italy.
authors: Massimo
authors: M
authors: Dominici
authors: INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France. Francoise.Redini@univ-nantes.fr.|Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France. Francoise.Redini@univ-nantes.fr.
authors: Françoise
authors: F
authors: Redini
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D064593:Heterografts; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D012512:Sarcoma, Ewing / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; D020169:Caspases
keywords: Ewing sarcoma; MSC; TRAIL; microenvironment; resistance