脑胶质瘤血管组分的起源

多形性胶质瘤母细胞瘤（GBM）是高度恶性、预后差的原发性脑肿瘤，具有侵袭性高和血供丰富的特点。但靶向血管内皮以协同治疗GBM的临床研究均告失败。有研究发现胶质瘤干细胞可以分化产生血管内皮细胞和壁细胞（mural cells）以支持肿瘤生长和侵袭。本课题组前期研究发现部分干性分子能同时标记胶质瘤干细胞和壁细胞，但肿瘤移植实验和体内谱系追踪研究发现胶质瘤干细胞不能产生壁细胞和内皮细胞。将在此基础上应用谱系追踪、三维图像重构、流式细胞分析、肿瘤干细胞体外分化和颅内成瘤等方法阐明胶质瘤血管内皮细胞和壁细胞的起源；并用转录组分析胶质瘤血管组分的分子特征，确定胶质瘤血管组分支持肿瘤生长和侵袭的分子基础；进一步探索干预肿瘤细胞、血管内皮细胞和壁细胞交互信号对于胶质瘤发生、生长和侵袭的作用。本研究将加深对于胶质瘤发生发展的认识，并有助于开发新的治疗手段。

Glioblastoma multiforme (GBM) are malignant primary brain tumors with properties of highly invasive and abundant blood supply. However, previous clinical studies targeting endothelial cells to treat GBMs all failed. Previous studies indicated glioma stem cells might give rise to vascular endothelial cells (ECs) and mural cells to support tumor growth and invasion. Our previous study found some stem-cell markers can label both glioma stem cells and mural cells. However, we showed glioma stem cells couldn’t differentiate into ECs and mural cells using xenografting and in vivo lineage-tracing experiments. We plan to further delineate the origin of glioma vascular cells utilizing lineage-tracing, three-dimensional image reconstruction, flow cell cytometry, in vitro differentiation and intracranial xenografting. Moreover, molecular basis for supporting tumor growth and invasion by vascular cells will be extensively studied using transcriptome analysis followed by cell sorting. Finally, the roles of signaling between tumor cells, ECs and mural cells in tumorigenesis and invasion will be investigated. This study would advance our understanding on gliomagenesis and facilitate novel therapeutic means.