Doublecortin is preferentially expressed in invasive human brain tumors
Doublecortin is preferentially expressed in invasive human brain tumors
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DOI：
10.1007/s00401-005-1070-0
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发表时间：
2005-11-01
影响因子：
12.7
通讯作者：
Ross, AH
中科院分区：
文献类型：
--
作者：
Daou, MC;Smith, TW;Ross, AH
双皮质素（DCX）是大脑皮层发育过程中神经母细胞迁移所必需的。DCX是一种微管相关蛋白，在细胞运动中发挥作用。这些事实使我们假设DCX在侵袭性脑肿瘤中增加。在69例神经上皮来源的石蜡包埋脑肿瘤中评估DCX表达。此外，小鼠脑室管膜下区和齿状回切片用作免疫染色的阳性对照，并通过肽中和证明抗体染色的特异性。DCX在高级别浸润性肿瘤（胶质母细胞瘤，n=11;间变性星形细胞瘤/少突星形细胞瘤，n=7;和髓母细胞瘤/PNET，n=6）和低级别浸润性肿瘤（少突胶质细胞瘤，n=3;和星形细胞瘤/少突星形细胞瘤，n=5）中均高度表达。然而，DCX在局限性肿瘤组中表达较低（毛细胞性星形细胞瘤，n=6;室管膜瘤/室管膜下瘤，n=7;胚胎发育不良性神经上皮肿瘤，n=4;神经节细胞胶质瘤，n=2;脑膜瘤，n=9;神经鞘瘤，n=9）。经Cochran-Mantel-Haenszel统计学检验，边界组与高、低浸润组比较，差异均有统计学意义（P <0.0001）。我们的结论是，DCX是优先表达在侵袭性脑肿瘤。此外，DCX免疫染色在肿瘤边缘比中心强。对于这些肿瘤的一个子集，我们还检测了DCX mRNA和蛋白的北方和Western印迹。采用北方印迹、免疫荧光显微镜和Western印迹法检测胶质瘤细胞系中DCX mRNA和蛋白的表达。总的来说，免疫组化、Western印迹和北方印迹最终证实了人脑肿瘤中DCX的表达。
Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular zone and dentate gyrus were used as positive controls for immunostaining, and specificity of antibody staining was demonstrated by peptide neutralization. DCX was highly expressed in both high-grade invasive tumors (glioblastoma, n=11; anaplastic astrocytoma/oligoastrocytoma, n=7; and medulloblastoma/PNET, n=6) and low-grade invasive tumors (oligodendroglioma, n=3; and astrocytoma/oligoastrocytoma, n=5). However, DCX was less intensely expressed in the circumscribed group of tumors (pilocytic astrocytoma, n=6; ependymoma/subependymoma, n=7; dysembryoplastic neuroepithelial tumor, n=4; ganglioglioma, n=2; meningioma, n=9; and schwannoma, n=9). By the Cochran-Mantel-Haenszel statistical test, the circumscribed group was significantly different from both the high-grade invasive group (P < 0.0001) and the low-grade invasive group (P < 0.0001). We conclude that DCX is preferentially expressed in invasive brain tumors. In addition, DCX immunostaining was stronger at the margin of the tumor than at the center. For a subset of these tumors, we also detected DCX mRNA and protein by Northern and Western blotting. DCX mRNA and protein was detected in glioma cell lines by Northern blotting, immunofluorescence microscopy and Western blotting. Collectively, the immunohistochemistry, Western blots and Northern blots conclusively demonstrate expression of DCX by human brain tumors.