Duntsch Christopher, Zhou Qihong, Weimar James D, Frankel Bruce, Robertson Jon H, Pourmotabbed Tayebeh
Department of Neurosurgery, The University of Tennessee Health Science Center, 847 Monroe Avenue, Suite 427, Memphis, TN 38163, USA.
J Neurooncol. 2005 Feb;71(3):245-55. doi: 10.1007/s11060-004-2156-6.
To investigate adult neural stem cell (NSC) biology in relation to glioma, the C6 glioma cell line was tagged with green fluorescent protein (GFP) and inoculated into the brain of adult rats. The in vivo biological response of the brain to glioma was studied using immunohistochemical analysis of the subventricular zone (SVZ), peritumoral areas, and glioma. Nestin immunoreactive cells were found infiltrating glioma, but the distribution of abnormal immunoreactivity was restricted to the dorsal and medial border of the tumor relative to the ipsilateral ventricle. The SVZ was found to be hypertrophic, hypercellular, and up-regulated nestin expression. Furthermore, a dense contiguous population of nestin immunoreactive cells could be found streaming from ipsilateral dorsal tip of the SVZ, tracking along the ventral margin of the corpus callosum, and fanning out to encompass and infiltrate the proximal tumor border. Although most cells were either nestin or glial fibrillary acidic protein (GFAP) immunoreactive in the SVZ and along the ventral margin of the corpus callosum, the number of cells co-expressing both markers increased proportionally as the tumor was approached so that the predominant cell population along the proximal tumor border was GFAP immunoreactive. Finally, we demonstrated that a significant proportion of cells found in areas of abnormal immunoreactivity were proliferating, especially in peritumoral areas. In summary, there is an induction of neuropoietic activity in a rat intracranial glioma model that results in an infiltration and accumulation of abnormal nestin and GFAP expressing cells with proliferative potential along the dorsal and medial border of intracranial C6 glioma.
为了研究与胶质瘤相关的成体神经干细胞（NSC）生物学特性，将绿色荧光蛋白（GFP）标记的C6胶质瘤细胞系接种到成年大鼠脑中。通过对脑室下区（SVZ）、肿瘤周围区域和胶质瘤进行免疫组织化学分析，研究大脑对胶质瘤的体内生物学反应。发现巢蛋白免疫反应性细胞浸润胶质瘤，但异常免疫反应性的分布仅限于相对于同侧脑室的肿瘤背侧和内侧边界。发现SVZ肥大、细胞增多且巢蛋白表达上调。此外，可以发现密集连续的巢蛋白免疫反应性细胞群体从SVZ同侧背侧尖端流出，沿着胼胝体腹缘追踪，并散开以包围和浸润肿瘤近端边界。虽然在SVZ和胼胝体腹缘大多数细胞要么是巢蛋白免疫反应性的，要么是胶质纤维酸性蛋白（GFAP）免疫反应性的，但随着接近肿瘤，共表达这两种标记物的细胞数量成比例增加，因此沿着肿瘤近端边界的主要细胞群体是GFAP免疫反应性的。最后，我们证明在异常免疫反应区域发现的相当一部分细胞正在增殖，尤其是在肿瘤周围区域。总之，在大鼠颅内胶质瘤模型中存在神经发生活性的诱导，导致具有增殖潜能的异常巢蛋白和GFAP表达细胞沿着颅内C6胶质瘤的背侧和内侧边界浸润和积聚。
