Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells

Yoshitaka Miyagawa, Hajime Okita, Hideki Nakaijima, Yasuomi Horiuchi, Ban Sato, Tomoko Taguchi, Masashi Toyoda, Yohko U. Katagiri, Junichiro Fujimoto, Jun Ichi Hata, Akihiro Umezawa, Nobutaka Kiyokawa

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Abstract

Ewing's family tumor (EFT) is a rare pediatric tumor of unclear origin that occurs in bone and soft tissue. Specific chromosomal translocations found in EFT cause EWS to fuse to a subset of ets transcription factor genes (ETS), generating chimeric EWS/ETS proteins. These proteins are believed to play a crucial role in the onset and progression of EFT. However, the mechanisms responsible for the EWS/ETS-mediated onset remain unclear. Here we report the establishment of a tetracycline-controlled EWS/ETS-inducible system in human bone marrow-derived mesenchymal progenitor cells (MPCs). Ectopic expression of both EWS/FLI1 and EWS/ERG proteins resulted in a dramatic change of morphology, i.e., from a mesenchymal spindle shape to a small round-to-polygonal cell, one of the characteristics of EFT. EWS/ETS also induced immunophenotypic changes in MPCs, including the disappearance of the mesenchyme-positive markers CD10 and CD13 and the up-regulation of the EFT-positive markers CD54, CD99, CD117, and CD271. Furthermore, a prominent shift from the gene expression profile of MPCs to that of EFT was observed in the presence of EWS/ETS. Together with the observation that EWS/ETS enhances the ability of cells to invade Matrigel, these results suggest that EWS/ETS proteins contribute to alterations of cellular features and confer an EFT-like phenotype to human MPCs.

Original languageEnglish
Pages (from-to)2125-2137
Number of pages13
JournalMolecular and cellular biology
Volume28
Issue number7
DOIs
Publication statusPublished - 2008 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Miyagawa, Y., Okita, H., Nakaijima, H., Horiuchi, Y., Sato, B., Taguchi, T., Toyoda, M., Katagiri, Y. U., Fujimoto, J., Hata, J. I., Umezawa, A., & Kiyokawa, N. (2008). Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells. Molecular and cellular biology, 28(7), 2125-2137. https://doi.org/10.1128/MCB.00740-07