Ewing sarcoma cells secrete EWS/Fli-1 fusion mRNA via microvesicles

Masanori Tsugita; Nami Yamada; Shunsuke Noguchi; Kazunari Yamada; Hiroshi Moritake; Katsuji Shimizu; Yukihiro Akao; Takatoshi Ohno

doi:10.1371/journal.pone.0077416

Ewing sarcoma cells secrete EWS/Fli-1 fusion mRNA via microvesicles

PLoS One. 2013 Oct 4;8(10):e77416. doi: 10.1371/journal.pone.0077416. eCollection 2013.

Authors

Masanori Tsugita¹, Nami Yamada, Shunsuke Noguchi, Kazunari Yamada, Hiroshi Moritake, Katsuji Shimizu, Yukihiro Akao, Takatoshi Ohno

Affiliation

¹ Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan ; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu, Gifu, Japan.

Abstract

Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients. Recently, it was validated that cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids, and that these MVs contain a selected set of tumor-related proteins and high levels of mRNAs and miRNAs. In this present study, we detected the Ewing sarcoma-specific EWS/Fli-1 mRNA in MVs from the culture medium of ES cell lines carrying t(11;22) (q24; 12). Also, we detected this fusion gene in approximately 40% of the blood samples from mice inoculated with xenografts of TC135 or A673 cells. These findings indicate the EWS/Fli-1 mRNA in MVs might be a new non-invasive diagnostic marker for specific cases of Ewing sarcoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Biological Transport
Cell Line, Tumor
Disease Models, Animal
Extracellular Space / metabolism
Heterografts
Humans
Mice
Oncogene Proteins, Fusion / chemistry
Oncogene Proteins, Fusion / genetics*
Oncogene Proteins, Fusion / metabolism*
Proto-Oncogene Protein c-fli-1 / chemistry
Proto-Oncogene Protein c-fli-1 / genetics*
Proto-Oncogene Protein c-fli-1 / metabolism*
RNA, Messenger / chemistry
RNA, Messenger / metabolism*
RNA-Binding Protein EWS / chemistry
RNA-Binding Protein EWS / genetics*
RNA-Binding Protein EWS / metabolism*
Sarcoma, Ewing / genetics*
Sarcoma, Ewing / metabolism*
Secretory Vesicles / metabolism*

Substances

EWS-FLI fusion protein
Oncogene Proteins, Fusion
Proto-Oncogene Protein c-fli-1
RNA, Messenger
RNA-Binding Protein EWS

Grants and funding

The work was supported by a grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.