TMIC-65. DISSECTING THE EXPRESSION AND FUNCTION OF ANGIOPOIETIN-1 IN BRAIN TUMORS

Abstract

Abstract Angiopoietin-1 (Angpt1) is a secreted protein that can promote angiogenesis and vascular stability in development and certain disease states through activation of the Tie2 receptor. However, little is known about its expression or function across brain tumor types. Surveying its expression across pediatric and adult brain tumors we show Angpt1 is upregulated in glial brain tumors, including high-grade gliomas and ependymomas, and that expression patterns correlate with cell-type expression patters we recently described in the normal developing and adult brain. To examine the cell type and location of Angpt1 expression within tumors we have generated electroporation based high-grade glioma and ependymoma mouse models in Angpt1-GFP reporter knock-in mice. Angpt1-GFP expression is found mainly in tumor cells within both tumor models, with varying expression in high-grade glioma models based on driver mutations and molecular subtype. Single-cell transcriptomic studies in these mouse models are underway to further delineate expression across tumor and non-tumor cell types. Moreover, we are leveraging this flexible electroporation-based mouse brain tumor modeling platform to examine Angpt1 function within brain tumors. Preliminary data shows that including a DNA plasmid encoding Cre-recombinase induces recombination and loss of Angpt1 in our electroporation-based brain tumor models, and ongoing studies aim to delineate its function in tumor pathogenesis, including tumor angiogenesis and blood-brain barrier function.