title: First identification of Ewing's sarcoma-derived extracellular vesicles and exploration of their biological and potential diagnostic implications.
abstract: BACKGROUND
  Exosomes are small RNA- and protein-containing extracellular vesicles (EVs) that are thought to mediate hetero- and homotypic intercellular communication between normal and malignant cells.Tumour-derived exosomes are believed to promote re-programming of the tumour-associated stroma to favour tumour growth and metastasis. Currently, exosomes have been intensively studied in carcinomas. However, little is known about their existence and possible role in sarcomas.
  
  
  RESULTS
  Here, we report on the identification of vesicles with exosomal features derived from Ewing's sarcoma(ES), the second most common soft-tissue or bone cancer in children and adolescents. ES cell line-derived EV shave been isolated by ultracentrifugation and analysed by flow-cytometric assessment of the exosome-associated proteins CD63 and CD81 as well as by electron microscopy. They proved to contain ES-specific transcripts including EWS-FLI1, which were suitable for the sensitive detection of ES cell line-derived exosomes by qRT-PCRin a pre-clinical model for patient plasma. Microarray analysis of ES cell line-derived exosomes revealed that they share a common transcriptional signature potentially involved in G-protein-coupled signalling, neurotransmitter signalling and stemness.
  
  
  CONCLUSIONS
  In summary, our results imply that ES-derived exosomes could eventually serve as biomarkers for minimal residual disease diagnostics in peripheral blood and prompt further investigation of their potential biological role in modification of the ES-associated microenvironment
authors.affiliation: Children's Cancer Research Center, Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, 80804 Munich, Germany.
authors.forename: Isabella V
authors.initials: IV
authors.lastname: Miller
authors.forename: Graca
authors.initials: G
authors.lastname: Raposo
authors.forename: Ulrich
authors.initials: U
authors.lastname: Welsch
authors.forename: Olivia
authors.initials: O
authors.lastname: Prazeres da Costa
authors.forename: Uwe
authors.initials: U
authors.lastname: Thiel
authors.forename: Maria
authors.initials: M
authors.lastname: Lebar
authors.forename: Martina
authors.initials: M
authors.lastname: Maurer
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Bender
authors.forename: Irene
authors.initials: I
authors.lastname: von Luettichau
authors.forename: Günther H S
authors.initials: GH
authors.lastname: Richter
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.forename: Thomas G P
authors.initials: TG
authors.lastname: Grunewald
mesh_terms: D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000097:blood* / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1 / Q000097:blood* / Q000235:genetics; D034802:RNA-Binding Protein EWS / Q000097:blood* / Q000235:genetics; D012512:Sarcoma, Ewing / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D060225:Tetraspanin 28 / Q000097:blood* / Q000235:genetics; D060149:Tetraspanin 30 / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D060225:Tetraspanin 28; D060149:Tetraspanin 30
keywords: Biomarker; Ewing's sarcoma; Exosomes; Extracellular vesicles; Microarray