Analysis of glioma cell proliferation, invasion, and angiogenesis in glioma stem cell niche using animal glioma models

恶性胶质瘤的侵袭、血管生成和增殖是其基本特征和治疗失败的主要原因。这些特征被认为起源于胶质瘤干细胞的生态位。胶质瘤干细胞生态位的确定对胶质瘤的治疗具有重要意义。我们已经建立了两个动物模型，从组织学上概括了两种侵袭性和血管生成表型，即血管生成依赖性(J3T-1)和非依赖性(J3T-2)侵袭性，这两种表型也在人脑胶质母细胞瘤中观察到。接种表达GFP的J3T-1G细胞，建立裸鼠脑瘤模型。对这些动物胶质瘤的病理标本进行检查，以分析与胶质瘤干细胞生态位相关的增殖、侵袭和血管生成。J3T-1G肿瘤显示明显的血管生成，肿瘤边缘新生的血管周围有胶质瘤细胞聚集，用时间流逝成像监测大鼠脑胶质瘤切片培养的动态变化。血管周围可见J3T-1G细胞分裂。肿瘤细胞沿血管通道外间隙迁移。我们的结果表明，神经胶质瘤的壁龛存在于血管周围。组织学显示胶质瘤干细胞龛的微环境。

Invasion, angiogenesis, and proliferation of malignant gliomas are fundamental traits and major reasons for treatment failure. These traits are considered to originate from glioma stem cell niche. Delineation of glioma stem cell niche is important in establishing treatment for gliomas. We have established two animal models that histologically recapitulated two invasive and angiogenic phenotypes, namely angiogenesis-dependent (J3T-1) and .independent (J3T-2) invasion, also observed in human glioblastoma. GFP-expressing J3T-1G cells were inoculated to establish brain tumors in athymic rats. Pathological samples of these animal gliomas were examined to analyze proliferation, invasioin, and angiogenesis in relation to glioma stem cell niche. J3T-1G tumor showed remarkable angiogenesis, and glioma cells clustered around newly developed vessels at tumor borders, For dynamic analysis, slice culture of rat brain harboring glioma was monitored by timelapse imaging. Cell division of J3T-1G cells were seen around vasculature. Tumor cells migrated along external space of vascular channel. Our results indicated glioma niche exists around vasculature. Microenvironment of glioma stem cell niche was shown histologically.