Extracellular vesicle-associated IGF2BP3 tunes Ewing sarcoma cell migration and affects PI3K/Akt pathway in neighboring cells

Cancer Gene Ther. 2023 Sep;30(9):1285-1295. doi: 10.1038/s41417-023-00637-8. Epub 2023 Jun 23.


Ewing sarcoma (EWS) is a challenging pediatric cancer characterized by vast intra-tumor heterogeneity. We evaluated the RNA-binding protein IGF2BP3, whose high expression correlates with a poor prognosis and an elevated tendency of metastases, as a possible soluble mediator of inter-cellular communication in EWS. Our data demonstrate that (i) IGF2BP3 is detected in cell supernatants, and it is released inside extracellular vesicles (EVs); (ii) EVs from IGF2BP3-positive or IGF2BP3-negative EWS cells reciprocally affect cell migration but not the proliferation of EWS recipient cells; (iii) EVs derived from IGF2BP3-silenced cells have a distinct miRNA cargo profile and inhibit the PI3K/Akt pathway in recipient cells; (iv) the 11 common differentially expressed miRNAs associated with IGF2BP3-positive and IGF2BP3-negative EVs correctly group IGF2BP3-positive and IGF2BP3-negative clinical tissue specimens. Overall, our data suggest that IGF2BP3 can participate in the modulation of phenotypic heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Child
  • Extracellular Vesicles* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Oncogene Proteins, Fusion / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sarcoma, Ewing* / genetics
  • Sarcoma, Ewing* / metabolism
  • Sarcoma, Ewing* / pathology


  • Oncogene Proteins, Fusion
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • IGF2BP3 protein, human