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Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Aberrant Hedgehog (Hh) signaling is characteristic of the embryonal subtype (ERMS) and of fusion-negative alveolar RMS. In the mouse, ERMS-like tumors can be induced by mutations in the Hh receptor Patched1 (Ptch). As in huma...

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Autores principales: Uhmann, Anja, Niemann, Hannah, Lammering, Bérénice, Henkel, Cornelia, Heß, Ina, Rosenberger, Albert, Dullin, Christian, Schraepler, Anke, Schulz-Schaeffer, Walter, Hahn, Heidi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329653/
https://www.ncbi.nlm.nih.gov/pubmed/22550417
http://dx.doi.org/10.1155/2012/357040
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author Uhmann, Anja
Niemann, Hannah
Lammering, Bérénice
Henkel, Cornelia
Heß, Ina
Rosenberger, Albert
Dullin, Christian
Schraepler, Anke
Schulz-Schaeffer, Walter
Hahn, Heidi
author_facet Uhmann, Anja
Niemann, Hannah
Lammering, Bérénice
Henkel, Cornelia
Heß, Ina
Rosenberger, Albert
Dullin, Christian
Schraepler, Anke
Schulz-Schaeffer, Walter
Hahn, Heidi
author_sort Uhmann, Anja
collection PubMed
description Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Aberrant Hedgehog (Hh) signaling is characteristic of the embryonal subtype (ERMS) and of fusion-negative alveolar RMS. In the mouse, ERMS-like tumors can be induced by mutations in the Hh receptor Patched1 (Ptch). As in humans these tumors show increased Hh pathway activity. Here we demonstrate that the treatment with the active form of vitamin D(3), calcitriol, inhibits Hh signaling and proliferation of murine ERMS in vivo and in vitro. Concomitantly, calcitriol activates vitamin D receptor (Vdr) signaling and induces tumor differentiation. In addition, calcitriol inhibits ERMS growth in Ptch-mutant mice, which is, however, a rather late response. Taken together, our results suggest that exogenous supply of calcitriol could be beneficial in the treatment of RMS, especially in those which are associated with aberrant Hh signaling activity.
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spelling pubmed-33296532012-05-01 Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma Uhmann, Anja Niemann, Hannah Lammering, Bérénice Henkel, Cornelia Heß, Ina Rosenberger, Albert Dullin, Christian Schraepler, Anke Schulz-Schaeffer, Walter Hahn, Heidi Sarcoma Research Article Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Aberrant Hedgehog (Hh) signaling is characteristic of the embryonal subtype (ERMS) and of fusion-negative alveolar RMS. In the mouse, ERMS-like tumors can be induced by mutations in the Hh receptor Patched1 (Ptch). As in humans these tumors show increased Hh pathway activity. Here we demonstrate that the treatment with the active form of vitamin D(3), calcitriol, inhibits Hh signaling and proliferation of murine ERMS in vivo and in vitro. Concomitantly, calcitriol activates vitamin D receptor (Vdr) signaling and induces tumor differentiation. In addition, calcitriol inhibits ERMS growth in Ptch-mutant mice, which is, however, a rather late response. Taken together, our results suggest that exogenous supply of calcitriol could be beneficial in the treatment of RMS, especially in those which are associated with aberrant Hh signaling activity. Hindawi Publishing Corporation 2012 2012-02-21 /pmc/articles/PMC3329653/ /pubmed/22550417 http://dx.doi.org/10.1155/2012/357040 Text en Copyright © 2012 Anja Uhmann et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Uhmann, Anja
Niemann, Hannah
Lammering, Bérénice
Henkel, Cornelia
Heß, Ina
Rosenberger, Albert
Dullin, Christian
Schraepler, Anke
Schulz-Schaeffer, Walter
Hahn, Heidi
Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma
title Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma
title_full Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma
title_fullStr Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma
title_full_unstemmed Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma
title_short Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma
title_sort calcitriol inhibits hedgehog signaling and induces vitamin d receptor signaling and differentiation in the patched mouse model of embryonal rhabdomyosarcoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329653/
https://www.ncbi.nlm.nih.gov/pubmed/22550417
http://dx.doi.org/10.1155/2012/357040
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