1. Extracellular vesicle-associated IGF2BP3 tunes Ewing sarcoma cell migration and affects PI3K/Akt pathway in neighboring cells.
- Author
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Mancarella C, Giusti V, Caldoni G, Laginestra MA, Parra A, Toracchio L, Giordano G, Roncuzzi L, Piazzi M, Blalock W, Columbaro M, De Feo A, and Scotlandi K
- Subjects
- Child, Humans, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Oncogene Proteins, Fusion genetics, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins c-akt metabolism, Extracellular Vesicles metabolism, Sarcoma, Ewing genetics, Sarcoma, Ewing metabolism, Sarcoma, Ewing pathology
- Abstract
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., (© 2023. The Author(s).)
- Published
- 2023
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