The difficulty in treatment of glioblastoma is a consequence of its natural infiltrative growth and the existence of a population of therapy-resistant glioma cells that contribute to growth and recurrence. To identify cells more likely to have these properties, we examined the expression in tumor specimens of several protein markers important for glioma progression including the intermediate filament protein, Nestin (NES), a glucose transporter (Glut1/SLC2A1), the glial lineage marker, glial fibrillary acidic protein, and the proliferative indicator, Ki-67. We also examined the expression of von Willebrand factor, a marker for endothelial cells as well as the macrophage/myeloid markers CD163 and CD15. Using a multicolor immunofluorescence and hematoxylin and eosin staining approach with archival formalin-fixed, paraffin embedded tissue from primary, recurrent, and autopsy IDH1 wildtype specimens combined with high-resolution tissue image analysis, we have identified highly proliferative NES(+)/Glut1(–) cells that are preferentially perivascular. In contrast, Glut1(+)/NES(–) cells are distant from blood vessels, show low proliferation, and are preferentially located at the borders of pseudopalisading necrosis. We hypothesize that Glut1(+)/NES(–) cells would be naturally resistant to conventional chemotherapy and radiation due to their low proliferative capacity and may act as a reservoir for tumor recurrence.

中文翻译：

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胶质母细胞瘤包含拓扑不同的增殖和代谢定义的巢蛋白和 Glut1 表达细胞亚群

胶质母细胞瘤的治疗困难是其自然浸润性生长和存在导致生长和复发的抗治疗胶质瘤细胞群的结果。为了鉴定更可能具有这些特性的细胞，我们检查了肿瘤标本中几种对胶质瘤进展很重要的蛋白质标志物的表达，包括中间丝蛋白巢蛋白 (NES)、葡萄糖转运蛋白 (Glut1/SLC2A1)、胶质谱系标志物、胶质纤维酸性蛋白和增殖指示剂 Ki-67。我们还检测了血管性血友病因子（一种内皮细胞标记物）以及巨噬细胞/骨髓标记物 CD163 和 CD15 的表达。使用多色免疫荧光和苏木精和伊红染色方法，档案福尔马林固定，来自原发性、复发性和尸检 IDH1 野生型标本的石蜡包埋组织结合高分辨率组织图像分析，我们已经确定了优先位于血管周围的高度增殖的 NES(+)/Glut1(-) 细胞。相反，Glut1(+)/NES(-)细胞远离血管，增殖率低，优先位于假栅栏坏死边缘。我们假设 Glut1(+)/NES(–) 细胞由于其低增殖能力而对常规化学疗法和放射线具有天然抗性，并且可能作为肿瘤复发的储存库。Glut1(+)/NES(-)细胞远离血管，增殖率低，优先位于假栅栏坏死边缘。我们假设 Glut1(+)/NES(–) 细胞由于其低增殖能力而对常规化学疗法和放射线具有天然抗性，并且可能作为肿瘤复发的储存库。Glut1(+)/NES(-)细胞远离血管，增殖率低，优先位于假栅栏坏死边缘。我们假设 Glut1(+)/NES(–) 细胞由于其低增殖能力而对常规化学疗法和放射线具有天然抗性，并且可能作为肿瘤复发的储存库。