Department of neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
J Exp Clin Cancer Res. 2010 Oct 28;29(1):138. doi: 10.1186/1756-9966-29-138.
Gliomas represent the most common primary malignant brain tumors, yet little is known about the molecular pathogenesis of these tumors. The highly-regulated Wnt signal transduction pathway is essential for normal developmental processes, and defects in the pathway are closely linked to oncogenesis. Dickkopf-1 (DKK-1) is a secreted protein that acts as a potent inhibitor of the Wnt pathway. The aim of this study was to examine the expression profile of DKK-1 gene in human glioma and its association with tumor malignancy.
We determined the expression levels of DKK-1 transcript and protein in 12 glioblastoma cell lines, medulloblastoma cells, low-grade glioma cells, and human astrocyte cells by semiquantitative RT-PCR and ELISA. A total of 47 tumor biopsy specimens and 11 normal brain tissue samples from patients with cerebral trauma internal decompression were embedded in paraffin blocks and used for immunostaining. Twenty-six primary tumors and 7 corresponding brain samples were stored in liquid nitrogen and used for RT-PCR. We further examined serologic concentrations and cerebral fluid levels of DKK-1 in patients with tumors.
DKK-1 could only be detected in 12 human glioblastoma cell lines, not in a panel of other tumor and normal cell lines. The difference between glioma patients and healthy individuals was significant. Kendall's tau-c association analysis also revealed the increased DKK-1 protein expression in tumor tissues of higher pathologic classification. The levels of cerebral fluid DKK-1 protein were significantly higher in glioma patients than in healthy donors or in neuronal benign tumor patients, suggesting that the DKK-1 molecule in cerebral fluids can be applicable to detect the presence of glioma and be developed as a novel prognostic treatment.
The Wnt antagonist DKK-1 gene may have important roles in glioma tumorigenesis and act as a novel biomarker in human malignant glioblastoma.
神经胶质瘤是最常见的原发性恶性脑肿瘤，但人们对这些肿瘤的分子发病机制知之甚少。高度调控的 Wnt 信号转导途径对于正常的发育过程至关重要，而该途径的缺陷与肿瘤发生密切相关。Dickkopf-1（DKK-1）是一种分泌蛋白，可作为 Wnt 途径的有效抑制剂。本研究旨在研究 DKK-1 基因在人神经胶质瘤中的表达谱及其与肿瘤恶性程度的关系。
我们通过半定量 RT-PCR 和 ELISA 测定了 12 种神经胶质瘤细胞系、髓母细胞瘤细胞、低级别神经胶质瘤细胞和人星形胶质细胞中 DKK-1 转录本和蛋白的表达水平。将 47 例脑外伤减压患者的肿瘤活检标本和 11 例正常脑组织标本包埋在石蜡块中进行免疫染色。26 例原发性肿瘤和 7 例相应的脑标本储存在液氮中用于 RT-PCR。我们还进一步检查了患者血清和脑脊液中 DKK-1 的浓度。
DKK-1 仅在 12 个人神经胶质瘤细胞系中被检测到，而在其他肿瘤和正常细胞系中则未被检测到。胶质瘤患者与健康个体之间的差异具有统计学意义。Kendall's tau-c 关联分析也显示，病理分级较高的肿瘤组织中 DKK-1 蛋白表达增加。与健康供体或神经良性肿瘤患者相比，胶质瘤患者脑脊液中 DKK-1 蛋白水平显著升高，提示脑脊液中的 DKK-1 分子可用于检测胶质瘤的存在，并可作为一种新的预后治疗方法。
Wnt 拮抗剂 DKK-1 基因可能在神经胶质瘤发生中起重要作用，并可作为人类恶性神经胶质瘤的新型生物标志物。
