Department of Neurosurgery, University Hospital, Liebigstr. 20, D-04103 Leipzig, Germany.
Transl Oncol. 2009 Aug 18;2(3):117-20. doi: 10.1593/tlo.09115.
The hallmarks of human malignant gliomas are their marked invasiveness and vascularity. Because angiogenesis and tumor invasion have been associated with extracellular matrix degradation and intercellular tight junctions, the involvement of zonulin in glioma biology is in the focus. We selected for histological examination five cases of glioblastoma WHO IV (nomenclature of the World Health Organization) and one case each from astrocytoma WHO III, meningioma WHO III, and meningioma WHO I as control samples. The meningioma WHO I is regarded as benign, whereas the meningioma WHO III is recognized as the transition form of malignant tumors in humans. The visualization of a newly designed antibody against human zonulin was studied in triple-labeling studies using fluorescence immunocytochemistry and compared with the expression of c-kit and glial fibrillary acidic protein in differently developed human gliomas. We found that increasing the expression of c-kit is accompanied by an increase of zonulin expression. Both are correlated to the degree of malignancy of human brain tumors. The expression of zonulin is correlated to the degradation of the blood-brain barrier as revealed by Griffonia simplicifolia lectin. In differently graded tumors, we found differently graded involvement of blood vessels in the tumor development, explaining patients' survival.
人类恶性神经胶质瘤的特征是其明显的侵袭性和血管生成。由于血管生成和肿瘤侵袭与细胞外基质降解和细胞间紧密连接有关，因此 zonulin 在神经胶质瘤生物学中的参与成为研究的焦点。我们选择了五个组织学检查的病例，包括 5 个世界卫生组织（WHO）IV 级的胶质母细胞瘤病例，1 个 III 级星形细胞瘤病例，1 个 III 级脑膜瘤病例和 1 个 I 级脑膜瘤病例作为对照样本。I 级脑膜瘤被认为是良性的，而 III 级脑膜瘤被认为是人类恶性肿瘤的过渡形式。我们使用荧光免疫细胞化学研究了针对人 zonulin 的新设计抗体的可视化，并与不同发展阶段的人类神经胶质瘤中 c-kit 和胶质纤维酸性蛋白的表达进行了比较。我们发现 c-kit 表达的增加伴随着 zonulin 表达的增加。两者都与人类脑肿瘤的恶性程度相关。zonulin 的表达与血脑屏障的降解相关，这可以通过 Griffonia simplicifolia 凝集素揭示。在不同分级的肿瘤中，我们发现血管在肿瘤发展中的参与程度不同，这可以解释患者的生存情况。
