title: Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma.
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.
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Almazán-Moga
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Zarzosa
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Vidal
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Molist
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Irina
authors.initials: I
authors.lastname: Giralt
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Navarro
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Aroa
authors.initials: A
authors.lastname: Soriano
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Miguel F
authors.identifier: 0000-0003-0916-3618
authors.initials: MF
authors.lastname: Segura
authors.affiliation: Cellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Arantza
authors.initials: A
authors.lastname: Alfranca
authors.affiliation: Cellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.identifier: 0000-0001-7604-1640
authors.initials: J
authors.lastname: Garcia-Castro
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; Pediatric Oncology and Hematology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Sánchez de Toledo
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.identifier: 0000-0001-7692-6123
authors.initials: J
authors.lastname: Roma
authors.affiliation: Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; Pediatric Oncology and Hematology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Soledad
authors.identifier: 0000-0002-4712-9624
authors.initials: S
authors.lastname: Gallego