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，也是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。我们建立了两种动物模型，在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。独立的（J3T-2）侵袭，在人胶质母细胞瘤中也观察到。用表达gfp的J3T-1G细胞接种胸腺大鼠建立脑肿瘤。研究了这些动物胶质瘤的病理样本，分析了胶质瘤干细胞生态位与增殖、侵袭和血管生成的关系。J3T-1G肿瘤血管新生明显，胶质瘤细胞聚集在肿瘤边界新形成的血管周围，采用延时成像技术监测胶质瘤大鼠脑切片培养的动态分析。血管周围可见J3T-1G细胞分裂。肿瘤细胞沿血管外腔迁移。结果表明胶质瘤生态位存在于血管周围。组织学显示胶质瘤干细胞生态位的微环境。

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.