A live single-cell reporter assay links intratumor heterogeneity to metastatic proclivity in Ewing sarcoma.
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- doi: 10.1126/sciadv.abf9394
- issn: 2375-2548
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Field guides Keys (Identification guides) Identification guides Phenotypes Tumor spread Spread of cancer Dissemination of cancer Tumor metastasis Tumor dissemination Metastatic cancer Metastases Cancer--Dissemination Neoplasm metastasis Cancer metastasis Cancer--Metastasis Administration Forensic identification Genes--Expression Expressive behavior Populations, Cell Aggression (Psychology) Aggressive behavior Aggressiveness (Psychology)Citer ce document
T. Keskin et al., « A live single-cell reporter assay links intratumor heterogeneity to metastatic proclivity in Ewing sarcoma. », Serveur académique Lausannois, ID : 10.1126/sciadv.abf9394
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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.