A live single-cell reporter assay links intratumor heterogeneity to metastatic proclivity in Ewing sarcoma.

Details

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State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_16E18D416FE5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A live single-cell reporter assay links intratumor heterogeneity to metastatic proclivity in Ewing sarcoma.
Journal
Science advances
Author(s)
Keskin T., Rucci B., Cornaz-Buros S., Martin P., Fusco C., Broye L., Cisarova K., Perez E.M., Letovanec I., La Rosa S., Cherix S., Diezi M., Renella R., Provero P., Suvà M.L., Stamenkovic I., Riggi N.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
07/2021
Peer-reviewed
Oui
Volume
7
Number
27
Pages
eabf9394
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Targeting of the most aggressive tumor cell subpopulations is key for effective management of most solid malignancies. However, the metastable nature of tumor heterogeneity, which allows cells to transition between strong and weak tumorigenic phenotypes, and the lack of reliable markers of tumor-promoting properties hamper identification of the most relevant cells. To overcome these obstacles, we designed a functional microRNA (miR)-based live-cell reporter assay to identify highly tumorigenic cells in xenotransplants of primary Ewing sarcoma (EwS) 3D cultures. Leveraging the inverse relationship between cell pluripotency and miR-145 expression, we successfully separated highly tumorigenic, metastasis-prone (miR-145 <sup>low</sup> ) cells from poorly tumorigenic, nonmetastatic (miR-145 <sup>high</sup> ) counterparts. Gene expression and functional studies of the two cell populations identified the EPHB2 receptor as a prognostic biomarker in patients with EwS and a major promoter of metastasis. Our study provides a simple and powerful means to identify and isolate tumor cells that display aggressive behavior.
Pubmed
Web of science
Open Access
Yes
Create date
05/07/2021 6:56
Last modification date
24/07/2021 5:34
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