Regulation and function of the vascular niche in glioma recurrance

University Of California, San Francisco, San Francisco CA

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Abstract

A.2. Gene expression analysis of gliomas, the most common brain tumor in adults, identifies subtypes enriched for progenitor and NSC genes. Diffuse gliomas are divided into astrocytomas, oligodendrogliomas, and oligoastrocytomas. Among malignant gliomas, (oligodendroglioma grade 3, astrocytoma grade 3-4), oligodendroglioma shows the most favorable prognosis Gene expression studies demonstrate four subtypes of grade 4 glioma (glioblastoma multiforme or GBM). Oligodendrogliomas and a subgroup of proneural GBMs express oligodendrocyte progenitor cell (OPC)-related genes. In contrast, mesenchymal GBMs display genes associated with NSCs, and a microenvironment rich in vascular and immune cells. GBM subclasses show distinct signal transduction pathways. Proneural and mesenchymal GBM subtypes also persist in vitro, where mesenchymal GBMs are associated with TGFB-, integrin- and endothelial-signaling. In genetically engineered murine astrocytoma models, tumors can originate from SVZ NSCs. We and others have recently demonstrated that oligodendroglioma, the most proneural glioma, is derived from OPCs in white matter, partly explaining the favorable prognosis and response to chemotherapy. We propose that the cell of origin for glioma subtypes also influences response to therapy and composition of the tumor microenvironment.