Regulation and function of the vascular niche in glioma recurrance

A.2.神经胶质瘤是成人中最常见的脑肿瘤，其基因表达分析鉴定了富含祖细胞和NSC基因的亚型。弥漫性胶质瘤分为星形细胞瘤、少突胶质细胞瘤和少突星形细胞瘤。在恶性胶质瘤（少突胶质细胞瘤3级，星形细胞瘤3-4级）中，少突胶质细胞瘤显示出最有利的预后。基因表达研究证实了4级胶质瘤的四种亚型（多形性胶质母细胞瘤或GBM）。少突胶质细胞瘤和前神经GBM亚群表达少突胶质细胞祖细胞（OPC）相关基因。相反，间充质GBM显示与NSC相关的基因，以及富含血管和免疫细胞的微环境。GBM亚类显示不同的信号转导途径。原神经和间充质GBM亚型也在体外持续存在，其中间充质GBM与TGFB-、整合素-和内皮-信号传导相关。在基因工程改造的鼠星形细胞瘤模型中，肿瘤可以起源于SVZ NSC。我们和其他人最近证实，少突胶质细胞瘤是最常见的神经胶质瘤，来源于白色物质中的OPCs，部分解释了其良好的预后和对化疗的反应。我们提出胶质瘤亚型的起源细胞也影响对治疗的反应和肿瘤微环境的组成。

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.