%0 Journal Article
%A Chan, Tiffany S Y
%A Picard, Daniel
%A Hawkins, Cynthia E
%A Lu, Mei
%A Pfister, Stefan
%A Korshunov, Andrey
%A Roussel, Martine F
%A Wechsler-Reya, Robert J
%A Henkin, Jack
%A Bouffet, Eric
%A Huang, Annie
%T Thrombospondin-1 mimetics are promising novel therapeutics for MYC-associated medulloblastoma.
%J Neuro-oncology advances
%V 3
%N 1
%@ 2632-2498
%C Oxford
%I Oxford University Press
%M DKFZ-2021-00462
%P vdab002
%D 2021
%X Medulloblastoma (MB) comprises four subtypes of which group 3 MB are the most aggressive. Although overall survival for MB has improved, the outcome of group 3 MB remains dismal. C-MYC (MYC) amplification or MYC overexpression which characterizes group 3 MB is a strong negative prognostic factor and is frequently associated with metastases and relapses. We previously reported that MYC expression alone promotes highly aggressive MB phenotypes, in part via repression of thrombospondin-1 (TSP-1), a potent tumor suppressor.In this study, we examined the potential role of TSP-1 and TSP-1 peptidomimetic ABT-898 in MYC-amplified human MB cell lines and two distinct murine models of MYC-driven group 3 MBs.We found that TSP-1 reconstitution diminished metastases and prolonged survival in orthotopic xenografts and promoted chemo- and radio-sensitivity via AKT signaling. Furthermore, we demonstrate that ABT-898 can recapitulate the effects of TSP-1 expression in MB cells in vitro and specifically induced apoptosis in murine group 3 MB tumor cells.Our data underscore the importance of TSP-1 as a critical tumor suppressor in MB and highlight TSP-1 peptidomimetics as promising novel therapeutics for the most lethal subtype of MB.
%K AKT (Other)
%K MYC (Other)
%K PI3K (Other)
%K TSP-1 (Other)
%K medulloblastoma (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33629064
%2 pmc:PMC7890793
%R 10.1093/noajnl/vdab002
%U https://inrepo02.dkfz.de/record/167615