Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors
Abstract
In this study, we have utilized glioma patients along with two unique murine glioma models: RCAS glioma model and Gl261 model to study various lineages of BMDCs during different stages of glial tumors. Importantly, we identified the unique the population VEGFR2+MDSCs in both patients and mice, which might be used as a surrogate marker for glioma diagnosis and prognosis in future. We have validated the changes of myeloid lineage and endothelial lineages during the progression of gliomas, and We observed bone marrow derived mesenchymal stem cells have only minimal effort on tumor progression. We have created inducible VEGFR2knockout system in RCAS-tva model. We demonstrated that bone marrow derived VEGFR2 signaling plays an important role in myeloid differentiation, and infiltration into tumor tissues. Deficiency of VEGFR2 in BMDCs led to impairment of tumor associated myeloid cells and delayed progression of low-grade glioma. Primary tumor up-regulates VEGFR2 in myeoloid cells throughID2/E2A pathway. This work has shown the importance of myeloid derived ID2/VEGFR2 signaling in low-grade to high-grade glioma transformation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2016
- Accession Number
- AD1039084
Entities
People
- Yujie Huang
Organizations
- Cornell University