title: Calcitriol inhibits hedgehog signaling and induces vitamin d receptor signaling and differentiation in the patched mouse model of embryonal rhabdomyosarcoma.
abstract: 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.
authors.affiliation: Institute of Human Genetics, University of Goettingen, 37073 Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Uhmann
authors.forename: Hannah
authors.initials: H
authors.lastname: Niemann
authors.forename: Bérénice
authors.initials: B
authors.lastname: Lammering
authors.forename: Cornelia
authors.initials: C
authors.lastname: Henkel
authors.forename: Ina
authors.initials: I
authors.lastname: Heß
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.forename: Anke
authors.initials: A
authors.lastname: Schraepler
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: Heidi
authors.initials: H
authors.lastname: Hahn