First identification of Ewing's sarcoma-derived extracellular vesicles and exploration of their biological and potential diagnostic implications

Biol Cell. 2013 Jul;105(7):289-303. doi: 10.1111/boc.201200086. Epub 2013 May 4.


Background information: 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

Keywords: Biomarker; Ewing's sarcoma; Exosomes; Extracellular vesicles; Microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cell Line, Tumor
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Humans
  • Oncogene Proteins, Fusion / blood*
  • Oncogene Proteins, Fusion / genetics
  • Proto-Oncogene Protein c-fli-1 / blood*
  • Proto-Oncogene Protein c-fli-1 / genetics
  • RNA-Binding Protein EWS / blood*
  • RNA-Binding Protein EWS / genetics
  • Sarcoma, Ewing / blood*
  • Sarcoma, Ewing / diagnosis
  • Sarcoma, Ewing / genetics
  • Soft Tissue Neoplasms / blood*
  • Soft Tissue Neoplasms / diagnosis
  • Soft Tissue Neoplasms / genetics
  • Tetraspanin 28 / blood*
  • Tetraspanin 28 / genetics
  • Tetraspanin 30 / blood*
  • Tetraspanin 30 / genetics


  • Biomarkers
  • EWS-FLI fusion protein
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • Tetraspanin 28
  • Tetraspanin 30