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TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models
Author(s) -
Guiho Romain,
Biteau Kevin,
Grisendi Giulia,
Taurelle Julien,
Chatelais Mathias,
Gantier Malika,
Heymann Dominique,
Dominici Massimo,
Redini Françoise
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30402
Subject(s) - mesenchymal stem cell , cancer research , stromal cell , sarcoma , ewing's sarcoma , medicine , tumor necrosis factor alpha , apoptosis , cytokine , stem cell , cell culture , immunology , biology , pathology , microbiology and biotechnology , biochemistry , genetics
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.