In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 7, No. 27 ( 2021-07-02)
Kurzfassung:
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 low ) cells from poorly tumorigenic, nonmetastatic (miR-145 high ) 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.
Materialart:
Online-Ressource
ISSN:
2375-2548
DOI:
10.1126/sciadv.abf9394
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2021
ZDB Id:
2810933-8
