Thyroid Hormone Induces Terminal Differentiation of Tumor Cells in Medulloblastoma

Dr. Zeng-jie Yang – The Research Institute of Fox Chase Cancer Center, Philadelphia, PA

Medulloblastoma (MB) is a common type of pediatric brain tumor. Despite the progress in current treatment including surgery, chemotherapy and radiotherapy, a significant proportion of patients still succumbs to this disease. Improved approaches to treat MB are urgently needed.

Previous studies found that tumor cells spontaneously become mature in human and mouse MB. After their maturation, tumor cells stop dividing so that tumor growth is inhibited, suggesting that MB can be treated by inducting tumor cell maturation. Thyroid hormone (TH) is normally produced and release from the thyroid gland, which controls metabolism, growth and brain development. In our preliminary studies, synthetic TH promoted MB cell maturation and repressed tumor cell growth in culture. These results suggest that TH can induce tumor cell maturation in MB. Here, we propose to investigate the molecular mechanism underlying TH induced maturation of MB cells, and test the therapeutic efficacies of synthetic TH in treating MB in mouse models.

Upon on the completion of our studies, we will establish the causal link between hypothyroidism (TH levels are low) and MB growth, and shed light on the molecular process by which TH stimulates tumor cell maturation. More importantly, our studies will prove that TH can effectively induce tumor cell maturation, and provide compelling evidence and rationale to use TH for MB treatment in clinics.