胶质母细胞瘤组织内血供丰富，但抗VEGF治疗的临床疗效并不理想。胶质瘤细胞中存在干细胞亚群，即胶质瘤干细胞（GSCs），具有较高的分化潜能。已有研究指出GSCs可分化为血管内皮细胞、周细胞等，即转分化，此现象提示GSCs可能由此参与肿瘤血管形成。我们初步研究通过对胶质母细胞瘤和瘤旁组织提取的周细胞进行转录组测序分析，发现胰岛素样生长因子结合蛋白-5（IGFBP5）在肿瘤源性周细胞中表达显著上调，体外研究进一步证实肿瘤微环境中的IGFBP5主要源于周细胞，并可被GSC细胞摄取进入细胞核。核内高IGFBP5水平的GSCs，其分化谱中血管周细胞标志物表达显著高于对照组。因此我们假设IGFBP5核转运影响GSCs的分化能力并参与肿瘤血管生成。为验证该假说，本课题将运用体外及体内的研究策略探究肿瘤源性周细胞诱导胶质瘤干细胞转分化的具体作用及分子机制，并为胶质瘤的抗血管治疗提供新的治疗靶点。

Glioblastoma (GBM) is the most malignant brain tumor and is highly resistant to intensive combination therapies and anti-VEGF therapies. Most current therapies targeting ECs are not curative and may transform tumor growth pattern toward a more invasive phenotype in GBMs. Glioma stem-like cells (GSCs), which possess self-renewing and differentiation properties, have been found to be differentiate into vascular endothelial cells and pericytes. Vascular pericytes play critical roles in various physiological contexts, including support of vascular structure and function, maintenance of blood-brain barrier, facilitation of vessel maturation, and initiation of vessel sprouting. Recent reports indicated that tumor vessels with less pericyte coverage appear more vulnerable to radiation and chemotherapy. In this study, high-throughput RNA sequencing and functional analysis were performed and IGFBP5 was demonstrated to be significantly elevated in pericytes from glioblastoma tissue. IGFBP5 was reported to be upregulated high grade glioma, yet the detailed mechanism is unknown. In our preliminary experiment, we transferred GSCs into regular culture dishes supplemented with 10%FBS. It was interesting to find that these serum-induced differentiated cells expressed mural cell marker SMA. Moreover, IGFBP5 was detected in both cytoplasm and nucleus of glioma cells. High expression of nuclear IGFBP5 in GSCs was associated with high level of pericyte markers in differentiated cells and elevated ability to form tubule in vitro. Based on these data, we hypothesized that pericyte-derived IGFBP5 contributes to the transdifferention from glioma stem cells into pericytes. To test this hypothesis, we will employ both in vitro and in vivo approaches to determine whether IGFBP5 nuclear translocation is necessary for vascular transdifferentiation of GSCs, and to elucidate the molecular pathways on how vascular differentiation is induced by IGFBP5 translocation. The study will enrich our understanding of IGFBP5 in glioma micro-environment and provide the novel sight for development of anti-angiogenic therapies in glioma.