title: ATL-derived exosomes modulate mesenchymal stem cells: potential role in leukemia progression.
abstract: BACKGROUND
  Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia. We hypothesized that the cargo of ATL-derived exosomes is transferred to MSCs and alter their functional behavior to support the establishment of the appropriate microenvironment for leukemia.
  
  
  RESULTS
  We showed that both ATL cells (C81 and HuT-102) and patient-derived cells released Tax-containing exosomes. The cargo of HuT-102-derived exosomes consisted of miR-21, miR-155 and vascular endothelial growth factor. We demonstrated that HuT-102-derived exosomes not only deliver Tax to recipient MSCs, but also induce NF-κB activation leading to a change in cellular morphology, increase in proliferation and the induction of gene expression of migration and angiogenic markers.
  
  
  CONCLUSIONS
  This study demonstrates that ATL-derived exosomes deliver Tax and other leukemia-related genes to MSCs and alter their properties to presumably create a more conducive milieu for leukemia. These findings highlight the contribution of leukemia-derived exosomes in cellular transformation and their potential value as biomarkers and targets in therapeutic strategies.
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Jamal
authors.initials: J
authors.lastname: El-Saghir
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Farah
authors.initials: F
authors.lastname: Nassar
authors.affiliation: Department of Internal Medicine and Experimental Pathology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.|Department of Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Nadim
authors.initials: N
authors.lastname: Tawil
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. me00@aub.edu.lb.
authors.forename: Marwan
authors.initials: M
authors.lastname: El-Sabban
mesh_terms: D000328:Adult; D001692:Biological Transport; D049109:Cell Proliferation; D018450:Disease Progression; D055354:Exosomes / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007938:Leukemia; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000503:physiopathology*; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D016328:NF-kappa B / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016356:Gene Products, tax; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A
keywords: Exosomes; Leukemia; MSCs; NF-κB; Niche; Tax; miRNA