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Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma Almazan Moga, Ana Zarzosa Martinez, Patricia Vidal Marin, Isaac Molist Muñoz, Carla Giralt Buch, Irina Soriano Fernández, Aroa Segura Ginard, Miguel Sánchez de Toledo Codina, Josep Roma Castanyer, Josep Gallego Melcón, Soledad Navarro Barea, Natalia Institut Català de la Salut [Almazán-Moga A, Zarzosa P, Vidal I, Molist C, Giralt I, Navarro N, Soriano A, Segura MF, Roma J] Grup de Recerca translacional en càncer infantil, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Sánchez de Toledo J, Gallego S] Grup de Recerca translacional en càncer infantil, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Oncologia i Hematologia Pediàtriques, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain Vall d'Hebron Barcelona Hospital Campus Tumors de parts toves Cèl·lules canceroses DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Muscle Tissue::Myosarcoma::Rhabdomyosarcoma ANATOMY::Cells::Stem Cells::Neoplastic Stem Cells DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma::Myosarcoma::Rhabdomyosarcoma ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::miosarcoma::rabdomiosarcoma ANATOMÍA::células::células madre::células madre neoplásicas ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::sarcoma::miosarcoma::rabdomiosarcoma Tumors dels teixits tous; Via Hedgehog; Rabdomiosarcoma Tumores de los tejidos blandos; Vía Hedgehog; Rabdomiosarcoma Soft tissue neoplasms; Hedgehog pathway; Rhabdomyosarcoma 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. The authors wish to thank Dr. Noel Monks (MedImmune) for the kind gift of the blocking antibody MEDI-5304 and Ms. Christine O’Hara for help with the English version of this manuscript. This work was supported by grants from Institut Català d’Oncologia (ICO), Instituto de Salud Carlos III (RTICC-RD12/0036/0016 and RD12/0036/0027; PI11/00740 and PI14/00647), Fundació A. BOSCH, and ajuts predoctorals VHIR. 2021-04-22T11:29:00Z 2021-04-22T11:29:00Z 2017-01-24 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Almazán-Moga A, Zarzosa P, Vidal I, Molist C, Giralt I, Navarro N, et al. Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma. Stem Cells Int. 2017;2017:7507380. 1687-9678 https://hdl.handle.net/11351/5902 10.1155/2017/7507380 28243259 000394217900001 eng Stem Cells International;2017 https://www.hindawi.com/journals/sci/2017/7507380/ info:eu-repo/grantAgreement/ES/1PN/2008-2011/RD12%2F0036%2F0016 info:eu-repo/grantAgreement/ES/2PN/2008-2011/PI11%2F00740 info:eu-repo/grantAgreement/ES/PE2013-2016/PI14%2F00647 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Hindawi Scientia