Altered metabolism of chemoresistant CD114+ medulloblastoma stem cells
Medulloblastoma is the most common malignant pediatric brain tumor. Up to 30% of medulloblastoma patients experience relapse; 5-year overall survival rate is less than 10% following relapse. Typical treatment regimen includes chemotherapy, radiation, and is accompanied by G-CSF adjuvant therapy to treat neutropenia. G-CSF binds to its receptor CD114, to promote cell proliferation and migration. 0.5 to 13% of medulloblastoma cells express the CD114 receptor and its expression has been linked to chemoresistance in medulloblastoma and other cancers. We hypothesized that chemoresistant CD114+ medulloblastoma stem cells exhibit altered energy metabolism which may serve as a potential therapeutic vulnerability. We performed untargeted metabolomics on DAOY CSF3R parental (1-2% CD114 expression), DAOY CSF3R over expression, and two DAOY CSF3R knockdown cell lines, with and without G-CSF treatment. We observed differences in metabolome between the cell lines. Further optimization of dosage and treatment time may identify additional metabolic changes induced by G-CSF. These altered metabolic processes may serve as therapeutic opportunities to target the chemoresistant CD114+ subpopulation of medulloblastoma.
