A research team at the Krembil Research Institute has discovered that a signaling pathway which controls blood vessel development in the brain has the ability to stop brain tumor formation in animal models of medulloblastoma, the most common malignant brain tumor diagnosed in children.
The findings, published in the journal eLife, are the first to show that blocking a signaling pathway called Norrin/Frizzled4 (Fzd4) drives changes in the support structures that surround pre-cancer cells and promotes medulloblastoma development in subjects that are genetically susceptible to the disease. Researchers found that blocking the Norrin/Fzd4 signal created more opportunities to form pre-cancerous growths and speed up tumour initiation. This work also suggests that an activated pathway may therefore block tumour formation.
“Our study brings a new dimension to our understanding of Medulloblastoma,” says Dr. Valerie Wallace, principal investigator of the study, Norrin/Frizzled4 Signaling in the Preneoplastic Niche Blocks Medulloblastoma Initiation, and Co-Director of the Donald K. Johnson Eye Institute.
The research, which was carried out in large part by Dr. Erin Bassett and Mr. Nicholas Tokarew, was initiated at the Ottawa Hospital Research Institute and continued at the Krembil Research Institute after Dr. Wallace relocated to Toronto. The discovery came from replication of a human condition called Gorlin Syndrome in lab experiments. People with Gorlin Syndrome have one copy of a tumour-suppressing gene instead of two, which makes them susceptible to medulloblastoma.
The team’s next step will be to investigate how the blood vessels impacted by Norrin/Fzd4 signaling communicate with pre-cancerous cells to make them more likely to become malignant.
Citation: Bassett, Erin A., Nicholas Tokarew, Ema A. Allemano, Chantal Mazerolle, Katy Morin, Alan J. Mears, Brian McNeill et al. “Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.” eLife 5 (2016): e16764.
Research funding: Canadian Cancer Society, Cancer Research Society
Adapted from press release by University Health Network Ca