Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in 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 resp...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/7507380 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556224082608128 |
|---|---|
| author | Ana Almazán-Moga Patricia Zarzosa Isaac Vidal Carla Molist Irina Giralt Natalia Navarro Aroa Soriano Miguel F. Segura Arantza Alfranca Javier Garcia-Castro José Sánchez de Toledo Josep Roma Soledad Gallego |
| author_facet | Ana Almazán-Moga Patricia Zarzosa Isaac Vidal Carla Molist Irina Giralt Natalia Navarro Aroa Soriano Miguel F. Segura Arantza Alfranca Javier Garcia-Castro José Sánchez de Toledo Josep Roma Soledad Gallego |
| author_sort | Ana Almazán-Moga |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d6b81fbcd77a4ae7bc53ac0055a40e73 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-d6b81fbcd77a4ae7bc53ac0055a40e732025-02-03T05:45:58ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/75073807507380Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in RhabdomyosarcomaAna Almazán-Moga0Patricia Zarzosa1Isaac Vidal2Carla Molist3Irina Giralt4Natalia Navarro5Aroa Soriano6Miguel F. Segura7Arantza Alfranca8Javier Garcia-Castro9José Sánchez de Toledo10Josep Roma11Soledad Gallego12Laboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainLaboratory of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, SpainRhabdomyosarcoma (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.http://dx.doi.org/10.1155/2017/7507380 |
| spellingShingle | Ana Almazán-Moga Patricia Zarzosa Isaac Vidal Carla Molist Irina Giralt Natalia Navarro Aroa Soriano Miguel F. Segura Arantza Alfranca Javier Garcia-Castro José Sánchez de Toledo Josep Roma Soledad Gallego Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma Stem Cells International |
| title | Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma |
| title_full | Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma |
| title_fullStr | Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma |
| title_full_unstemmed | Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma |
| title_short | Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma |
| title_sort | hedgehog pathway inhibition hampers sphere and holoclone formation in rhabdomyosarcoma |
| url | http://dx.doi.org/10.1155/2017/7507380 |
| work_keys_str_mv | AT anaalmazanmoga hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT patriciazarzosa hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT isaacvidal hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT carlamolist hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT irinagiralt hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT natalianavarro hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT aroasoriano hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT miguelfsegura hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT arantzaalfranca hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT javiergarciacastro hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT josesanchezdetoledo hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT joseproma hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma AT soledadgallego hedgehogpathwayinhibitionhamperssphereandholocloneformationinrhabdomyosarcoma |