Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting Glial Cells.

摘要

Medulloblastoma is the most common malignant pediatric brain tumor. Granule neuron precursors (GNPs) in developing cerebellum proliferate exponentially, and the misregulation of which has been linked to medulloblastoma formation. GNPs are unipotent and only give rise to granule neurons. However, using MADM, a mouse genetic mosaic model, we found that medulloblastoma contain glial cells that are trans-differentiated from transformed GNPs. Our preliminary data showed that specific ablation of tumor glia without harming tumor GNPs led to complete tumor remission, suggesting a tumor-supporting role for these trans-differentiated glia. Here we propose to analyze the tumor social behavior with two specific aims. First, we will investigate the tumor regressing process at the cellular level in vivo, and determine therapeutic parameters of glial ablation for medulloblastoma treatment. Second, we will investigate the molecular basis for glia-tumor crosstalk that sustains the tumor growth. In the past year, we have completed most of the work proposed in aim 1. Our data showed that the glial-ablation treatment not only results in complete remission free of relapses, but also remains quite effective for mice with late-stage tumors. These findings are particularly encouraging since they point to great potentials in targeting glial cells for treating medulloblastoma in human patients. patients.