Regulation and function of the vascular niche in glioma recurrance

A.2.胶质瘤是成人最常见的脑肿瘤，其基因表达分析确定了富含祖细胞和神经干细胞基因的亚型。弥漫性胶质瘤分为星形细胞瘤、少突胶质细胞瘤和少突胶质细胞瘤。在恶性胶质瘤(少突胶质细胞瘤3级、星形细胞瘤3-4级)中，少突胶质细胞瘤预后最好。基因表达研究显示4级胶质瘤有四种亚型(多形性胶质母细胞瘤或GBM)。少突胶质瘤和神经胶质细胞亚群表达少突胶质前体细胞(OPC)相关基因。相比之下，间充质基底膜显示与神经干细胞相关的基因，以及富含血管和免疫细胞的微环境。GBM亚类显示出不同的信号转导途径。神经和间充质基底膜亚型在体外也存在，其中间充质基底膜与TGFb、整合素和内皮信号有关。在基因工程小鼠星形细胞瘤模型中，肿瘤可以来自SVZ神经干细胞。我们和其他人最近证明，少突胶质瘤是最多的神经胶质瘤，起源于白质中的OPC，部分解释了良好的预后和对化疗的反应。我们认为，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.