Home > Publications database > Thrombospondin-1 mimetics are promising novel therapeutics for MYC-associated medulloblastoma. > print

001     167615
005     20240229133544.0
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037 _ _ |a DKFZ-2021-00462
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082 _ _ |a 610
100 1 _ |a Chan, Tiffany S Y
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245 _ _ |a Thrombospondin-1 mimetics are promising novel therapeutics for MYC-associated medulloblastoma.
260 _ _ |a Oxford
|c 2021
|b Oxford University Press
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a AKT
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650 _ 7 |a MYC
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650 _ 7 |a TSP-1
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650 _ 7 |a medulloblastoma
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700 1 _ |a Picard, Daniel
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700 1 _ |a Hawkins, Cynthia E
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700 1 _ |a Lu, Mei
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700 1 _ |a Pfister, Stefan
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700 1 _ |a Korshunov, Andrey
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700 1 _ |a Roussel, Martine F
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700 1 _ |a Wechsler-Reya, Robert J
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700 1 _ |a Henkin, Jack
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700 1 _ |a Bouffet, Eric
|b 9
700 1 _ |a Huang, Annie
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773 _ _ |a 10.1093/noajnl/vdab002
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|t Neuro-oncology advances
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