A stem cell protein promotes the recurrence of brain tumors in children

Malignant brain tumor-type medulloblastoma can become resistant to treatment, leading to relapse
.
Researchers at Uppsala University have discovered a protein that keeps tumor cells quiescent and insensitive
to radiation therapy.
The team hopes that the findings will eventually lead to better treatments
for those children who are at highest risk of recurrence.

Medulloblastoma is the most common malignant brain tumor in children and can usually be cured
with surgery, radiation and chemotherapy.
But a different type of medulloblastoma has an increased
risk of developing resistance to treatment.
This leads to relapses
that are strongly associated with increased mortality.

Certain cancer cells can avoid treatment, suggesting that there are biological factors inside cancer cells that can enhance their resistance to radiation
, etc.
In the current study, the team has shown that some cells in tumors don't divide as frequently as others, making them less sensitive
to radiation.
They also found an accumulation
of a particular protein, SOX9, in relapsed samples from patients who had surgery both before and after the relapse.
They then suspected that SOX9 was involved in the relapse process
.

"We found that a stem cell protein called SOX9 is highly active in rare cells in tumors, while cells with high SOX9 activity are dormant
.
SOX9 protects quiescent cancer cells from radiation
by temporarily inhibiting another protein that promotes cell division.
In our experiments knocking out SOX9 with CRISPR/Cas9 gene scissors, tumor cells lost the ability to relapse, suggesting that SOX9 is important in this process," said Fredrik Swartling of Uppsala University, who led the study
.

In animal models similar to patient recurrence, SOX9 increases the migration and metastasis
of cancer cells in the region within the spinal cord.
Cancer cells are also reprogrammed to avoid being recognized
by the immune system.
These are all contributing factors
to relapse.

The researchers further investigated how substances that inhibit SOX9 affect recurrence
in animal models.
Through bioinformatics analysis, they found drugs used in other treatments that unexpectedly had inhibitory effects
on relapsed SOX9.

"We hope our findings will lead to more specific treatments
for those SOX9-positive, slow-dividing cancer cells.
" Ultimately, it may improve the likelihood of treating children with medulloblastoma who are at highest risk of recurrence," said Anna Borgenvik, a postdoc on the research team, who conducted the therapeutic study
based on bioinformatics analysis developed by Holger Weishaupt, a researcher on the team.

The study was conducted
in collaboration with preclinical cancer treatment centers, scientific laboratories and pilot facilities sponsored by Uppsala University.