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Copyright © 2017 Ana Almazán-Moga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and can be divided into two main subtypes: embryonal (eRMS) and alveolar (aRMS). Among the cellular heterogeneity of tumors, the existence of a small fraction of cells called cancer stem cells (CSC), thought to be responsible for the onset and propagation of cancer, has been demonstrated in some neoplasia. Although the existence of CSC has been reported for eRMS, their existence in aRMS, the most malignant subtype, has not been demonstrated to date. Given the lack of suitable markers to identify this subpopulation in aRMS, we used cancer stem cell-enriched supracellular structures (spheres and holoclones) to study this subpopulation. This strategy allowed us to demonstrate the capacity of both aRMS and eRMS cells to form these structures and retain self-renewal capacity. Furthermore, cells contained in spheres and holoclones showed significant Hedgehog pathway induction, the inhibition of which (pharmacologic or genetic) impairs the formation of both holoclones and spheres. Our findings point to a crucial role of this pathway in the maintenance of these structures and suggest that Hedgehog pathway targeting in CSC may have great potential in preventing local relapses and metastases.

Details

Title
Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma
Author
Almazán-Moga, Ana; Zarzosa, Patricia; Vidal, Isaac; Molist, Carla; Giralt, Irina; Navarro, Natalia; Soriano, Aroa; Segura, Miguel F; Alfranca, Arantza; Garcia-Castro, Javier; Sánchez de Toledo, José; Roma, Josep; Gallego, Soledad
Publication year
2017
Publication date
2017
Publisher
John Wiley & Sons, Inc.
ISSN
1687966X
e-ISSN
16879678
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1865751203
Copyright
Copyright © 2017 Ana Almazán-Moga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.