Glioblastoma usually recurs after therapy consisting of surgery, radiotherapy, and chemotherapy. Recurrence is at least partly caused by glioblastoma stem cells (GSCs) that are maintained in intratumoral hypoxic peri-arteriolar microenvironments, or niches, in a slowly dividing state that renders GSCs resistant to radiotherapy and chemotherapy. Because the subventricular zone (SVZ) is a major niche for neural stem cells (NSCs) in the brain, we investigated whether GSCs are present in the SVZ at distance from the glioblastoma tumor. We characterized the SVZ of brains of seven glioblastoma patients using fluorescence immunohistochemistry and image analysis. NSCs were identified by CD133 and SOX2 but not CD9 expression, whereas GSCs were positive for all three biomarkers. NSCs were present in all seven samples and GSCs in six out of seven samples. The SVZ in all samples were hypoxic and expressed the same relevant chemokines and their receptors as GSC niches in glioblastoma tumors: stromal-derived factor-1α (SDF-1α), C-X-C receptor type 4 (CXCR4), osteopontin, and CD44. In conclusion, in glioblastoma patients, GSCs are present at distance from the glioblastoma tumor in the SVZ. These findings suggest that GSCs in the SVZ niche are protected against radiotherapy and chemotherapy and protected against surgical resection due to their distant localization and thus may contribute to tumor recurrence after therapy.

胶质母细胞瘤通常在包括外科手术，放射疗法和化学疗法的疗法后复发。复发至少部分是由胶质母细胞瘤干细胞（GSC）引起的，它在肿瘤内缺氧的小动脉周围微环境或壁ni中保持缓慢分裂状态，使GSC对放射疗法和化学疗法具有抵抗力。因为脑室下区（SVZ）是大脑中神经干细胞（NSC）的主要利基，所以我们调查了SVZ中距胶质母细胞瘤肿瘤的距离是否存在GSC。我们使用荧光免疫组织化学和图像分析表征了七个胶质母细胞瘤患者的大脑的SVZ。NSCs通过CD133和SOX2鉴定，但不通过CD9表达鉴定，而GSCs对所有三种生物标志物均为阳性。NSCs出现在所有七个样本中，GSC出现在七个样本中的六个样本中。所有样品中的SVZ都是低氧的，并且与胶质母细胞瘤肿瘤中的GSC壁expressed表达相同的相关趋化因子及其受体：基质衍生因子1α（SDF-1α），CXC受体4型（CXCR4），骨桥蛋白和CD44。总之，在胶质母细胞瘤患者中，GSC与SVZ中的胶质母细胞瘤距离较远。这些发现表明，由于其远处的定位，SVZ生态位中的GSC受到了放射疗法和化学疗法的保护，并受到了手术切除的保护，因此可能有助于治疗后肿瘤的复发。GSC存在于SVZ中距胶质母细胞瘤肿瘤一定距离的地方。这些发现表明，由于其远处的定位，SVZ生态位中的GSC受到了放射疗法和化学疗法的保护，并受到了手术切除的保护，因此可能有助于治疗后肿瘤的复发。GSC存在于SVZ中距胶质母细胞瘤肿瘤一定距离的地方。这些发现表明，由于其远处的定位，SVZ生态位中的GSC受到了放射疗法和化学疗法的保护，并受到了手术切除的保护，因此可能有助于治疗后肿瘤的复发。