Wnt activation as a therapeutic strategy in medulloblastoma

Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/β-catenin signaling.


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In vivo sample sizes were chosen for in vivo studies based on prior studies, which validated the minimum number of mice to determine a significant difference. This was determined at a minimum of 5 mice per treatment arm.
In vitro sample sizes were partly limited based on number of available primary cell lines and replicates were performed at least 3 times independently for each available cell line.
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All attempts at data replication were taken to confirm previous results.
For L807mts treatment, each litter of NOD-SCID mice were randomized (in order of transplantation to control and treatment group. Otherwise, samples were allocated randomly to experimental groups. Investigators were blinded to group allocation. Macroscopic and/or microscopic phenotypes prevented blinding during data collection and analysis. Note that full information on the approval of the study protocol must also be provided in the manuscript. Male and female laboratory NOD-SCID mice of at least 12 weeks of age were used. Mice were maintained in the animal facilities at the McMaster University Stem Cell Unit (SCU) within the Animal Facility (CAF). They were maintained in a pathogen-free, temperature-controlled, 12h light and dark cycle environment and were fed ad libitum No wild animals were used in this study No field-collected samples were used in this study All in vivo experiments were performed in accordance to the McMaster University Animal Research Ethics Board (AREB) approved protocols national guidelines and regulations.