title: Inhibition of autocrine secretion of myostatin enhances terminal differentiation in human rhabdomyosarcoma cells.
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.
authors: INRA, UMR 866-Differenciation Cellulaire et Croissance, 34060 Montpellier Cedex 1, France.
authors: Stéphanie
authors: S
authors: Ricaud
authors: Barbara
authors: B
authors: Vernus
authors: Michel
authors: M
authors: Duclos
authors: Henri
authors: H
authors: Bernardi
authors: Olli
authors: O
authors: Ritvos
authors: Gilles
authors: G
authors: Carnac
authors: Anne
authors: A
authors: Bonnieu
mesh_terms: D000906:Antibodies / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D055435:Myostatin; D012208:Rhabdomyosarcoma / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; C525911:MSTN protein, human; D055435:Myostatin; D016212:Transforming Growth Factor beta