title: Exosomes derived from embryonal and alveolar rhabdomyosarcoma carry differential miRNA cargo and promote invasion of recipient fibroblasts.
abstract: Rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue tumor, which exists in oncoprotein PAX-FOXO1 fusion positive and fusion negative subtypes, with the fusion-positive RMS being characterized by a more aggressive clinical behavior. Exosomes are small membranous vesicles secreted into body fluids by multiple cell types, including tumor cells, and have been implicated in metastatic progression through paracrine signaling. We characterized exosomes secreted by a panel of 5 RMS cell lines. Expression array analysis showed that, for both fusion-positive and fusion-negative cells, exosome miRNA clustered well together and to a higher extent than cellular miRNA. While enriched miRNA in exosomes of fusion-negative RMS cells were distinct from those of fusion-positive RMS cells, the most significant predicted disease and functions in both groups were related to processes relevant to cancer and tissue remodelling. Functionally, we found that RMS-derived exosomes exerted a positive effect on cellular proliferation of recipient RMS cells and fibroblasts, induced cellular migration and invasion of fibroblasts, and promoted angiogenesis. These findings show that RMS-derived exosomes enhance invasive properties of recipient cells, and that exosome content of fusion-positive RMS is different than that of fusion-negative RMS, possibly contributing to the different metastatic propensity of the two subtypes.
authors.affiliation: Department of Biology, Faculty of Science II, EDST, Lebanese University, Fanar, Lebanon.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Ghayad
authors.affiliation: Department of Biology, Faculty of Science II, EDST, Lebanese University, Fanar, Lebanon.|Department of Pediatric and Adolescent Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Ghina
authors.initials: G
authors.lastname: Rammal
authors.affiliation: Department of Pediatric and Adolescent Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Farah
authors.initials: F
authors.lastname: Ghamloush
authors.affiliation: Department of Pediatric and Adolescent Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hussein
authors.initials: H
authors.lastname: Basma
authors.affiliation: Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut, Lebanon.
authors.forename: Rihab
authors.initials: R
authors.lastname: Nasr
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Sciences II, EDST, Lebanese University, Fanar, Lebanon.
authors.forename: Mona
authors.initials: M
authors.lastname: Diab-Assaf
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Claude
authors.initials: C
authors.lastname: Chelala
authors.affiliation: Department of Pediatric and Adolescent Medicine, American University of Beirut, Beirut, Lebanon.|Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut, Lebanon.
authors.forename: Raya
authors.initials: R
authors.lastname: Saab
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D019899:Paracrine Communication; D012334:RNA, Neoplasm / Q000378:metabolism*; D018232:Rhabdomyosarcoma, Alveolar / Q000378:metabolism* / Q000473:pathology; D018233:Rhabdomyosarcoma, Embryonal / Q000378:metabolism* / Q000473:pathology
chemical_list: D035683:MicroRNAs; D012334:RNA, Neoplasm