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  • Original Paper
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Inhibition of autocrine secretion of myostatin enhances terminal differentiation in human rhabdomyosarcoma cells

Oncogene volume 22, pages 8221–8232 (2003)Cite this article

Abstract

Rhabdomyosarcomas (RMSs) are one of the most common solid tumor of childhood. Rhabdomyosarcoma (RMS) cells fail to both complete the skeletal muscle differentiation program and irreversibly exit the cell cycle as a consequence of an active repression exerted on the muscle-promoting factor MyoD. Myostatin is a negative regulator of normal muscle growth, we have thus studied its possible role in RMS cells. Here, we present evidence that overexpression of myostatin is a common feature of RMS since both subtypes of RMS (embryonal RD and alveolar Rh30 cells) express high levels of myostatin when compared to nontumoral skeletal muscle cells. Interestingly, we found that inactivation of myostatin through overexpression of antisense myostatin or of follistatin (a myostatin antagonist) constructs enhanced differentiation of RD cells. In addition, RD and Rh30 cells treated with blocking antimyostatin antibodies progress into the myogenic terminal differentiation program. Finally, our results suggest that high levels of myostatin could impair MyoD function in RMS cells. These results show that an autocrine myostatin loop contributes to maintain RMS cells in an undifferentiating stage and suggest that new therapeutic approaches could be exploited for the treatment of RMS based on inactivation of myostatin protein.

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Acknowledgements

We thank Francis Bacou for his continued interest and support for this work. We also thank Stephen Tapscott and Anne Fernandez for providing us with the human RMS cell lines and the rabbit polyclonal anti-cyclinA antibodies, respectively. We are equally indebted to Jean-Marc Brandolo and Xavier Cousin for their useful discussions. This work was supported by funds from the Institut National de la Recherche Agronomique (INRA) and the Ligue Nationale contre le Cancer, Comité Régional des Pyrénées Orientales. SR was successively the recipient of a doctoral fellowship from the Association pour la Recherche sur le Cancer, and from the Ligue Nationale contre le Cancer, Comité Régional des Pyrénées Orientales.

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Author notes

  1. Gilles Carnac and Anne Bonnieu: These two authors contributed equally to this work

Authors and Affiliations

  1. INRA, UMR 866-Differenciation Cellulaire et Croissance, Montpellier, 34060, Cedex 1, France

    Stéphanie Ricaud, Barbara Vernus, Henri Bernardi & Anne Bonnieu

  2. INRA, Station de Recherches Avicoles, Nouzilly Tours, 37380, France

    Michel Duclos

  3. Biomedicum Helsinki and Department of Bacteriology and Immunology, Programme for Developmental and Reproductive Biology, Haartman Institute, University of Helsinki, PO Box 63 (Haartmaninkatu 8), Helsinki, 00014, Finland

    Olli Ritvos

  4. CRBM, CNRS FRE 2593, 1919 Route de Mende, Montpellier, 34293, Cedex 5, France

    Gilles Carnac

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  1. Stéphanie Ricaud
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Correspondence to Anne Bonnieu.

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Ricaud, S., Vernus, B., Duclos, M. et al. Inhibition of autocrine secretion of myostatin enhances terminal differentiation in human rhabdomyosarcoma cells. Oncogene 22, 8221–8232 (2003). https://doi.org/10.1038/sj.onc.1207177

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