Targeting Cancer Stem-like Cells as an Approach to Defeating Cellular Heterogeneity in Ewing Sarcoma.

Détails

ID Serval
serval:BIB_C91522094EF9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Targeting Cancer Stem-like Cells as an Approach to Defeating Cellular Heterogeneity in Ewing Sarcoma.
Périodique
Cancer Research
Auteur(s)
Cornaz-Buros S., Riggi N., DeVito C., Sarre A., Letovanec I., Provero P., Stamenkovic I.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
74
Numéro
22
Pages
6610-6622
Langue
anglais
Notes
Publication types: Publication Status: ppublish
Résumé
Plasticity in cancer stem-like cells (CSC) may provide a key basis for cancer heterogeneity and therapeutic response. In this study, we assessed the effect of combining a drug that abrogates CSC properties with standard-of-care therapy in a Ewing sarcoma family tumor (ESFT). Emergence of CSC in this setting has been shown to arise from a defect in TARBP2-dependent microRNA maturation, which can be corrected by exposure to the fluoroquinolone enoxacin. In the present work, primary ESFT from four patients containing CD133(+) CSC subpopulations ranging from 3% to 17% of total tumor cells were subjected to treatment with enoxacin, doxorubicin, or both drugs. Primary ESFT CSC and bulk tumor cells displayed divergent responses to standard-of-care chemotherapy and enoxacin. Doxorubicin, which targets the tumor bulk, displayed toxicity toward primary adherent ESFT cells in culture but not to CSC-enriched ESFT spheres. Conversely, enoxacin, which enhances miRNA maturation by stimulating TARBP2 function, induced apoptosis but only in ESFT spheres. In combination, the two drugs markedly depleted CSCs and strongly reduced primary ESFTs in xenograft assays. Our results identify a potentially attractive therapeutic strategy for ESFT that combines mechanism-based targeting of CSC using a low-toxicity antibiotic with a standard-of-care cytotoxic drug, offering immediate applications for clinical evaluation.
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/12/2014 19:33
Dernière modification de la notice
20/08/2019 16:44
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