Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors
Annual rept. 1 Sep 2014 - 31 Aug 2015
CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
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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 VEGFR2MDSCs 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 VEGFR2 knockout 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 BMDCs through ID2E2A pathway. All of these findings may have implications to suppress the switch of low-grade to high-grade transformation, and predict the long-term survival.
- Anatomy and Physiology
- Medicine and Medical Research