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

Abstract

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

• Authors: Isabella V Miller, Graca Raposo, Ulrich Welsch, Olivia Prazeres da Costa, Uwe Thiel, Maria Lebar, Martina Maurer, Hans-Ulrich Bender, Irene von Luettichau, Günther H S Richter, Stefan Burdach, Thomas G P Grunewald
• Journal: Biology of the cell (Biol Cell) Vol. 105 Issue 7 Pg. 289-303 (Jul 2013) ISSN: 1768-322X [Electronic] England
• PMID: 23521563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Chemical References

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

Topics

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