Markus Schülke-Gerstenfeld, Karl Seeger

Summary

Rhabdomyosarcoma derives from skeletal muscle cell lineages and is the most common malignant soft-tissue tumor in children. The prognosis, especially in metastatic disease has not changed over the last 15 years and remains dismal. In this project, we will investigate the influence of the secreted growth factor myostatin and its antagonist follistatin on the development, differentiation, and growth of rhabdomyosarcoma cells. Myostatin belongs to the transforming growth factor (TGF) superfamily of secreted growth factors and negatively regulates muscle growth. Cells from permanent cell lines (RD- and Rh30-cells) and from primary sources (direct culture from explanted tumor tissue) will be incubated with myostatin and follistatin and subsequently investigated for markers of myogenic differentiation (Pax3, c-met, Lbx1, Myf5, MyoD, Myogenin, Mox2, Pax7 and myosin heavy chain, troponin T). Growth characteristics will be investigated through in vitro proliferation assays. In the past, others and we have shown that myostatin can suppress the growth of rhabdomyosarcoma cells in vitro. We will elaborate on these findings and test the effect of these growth factors on rhabdomyosracoma growth in vivo as a potential new therapeutic principle through simultaneous xenotransplantation of rhabdomyosracoma cells and of myostatin-producing CHO cells into athymic nude mice.