Book A A, Ranganathan S, Abounader R, Rosen E, Laterra J
Department of Neurology, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA.
Brain Res. 1999 Jul 3;833(2):173-80. doi: 10.1016/s0006-8993(99)01527-9.
Malignant gliomas are associated with a dysfunctional blood-tumor barrier (BTB) that causes substantial morbidity. Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth factor that correlates with glioma malignancy and has several biological properties that suggest a role in enhancing blood-glioma barrier permeability. In this study, we examined the effects of glioma cell SF/HGF expression on BTB permeability to horseradish peroxidase (HRP). Fischer 344 rats bearing intrastriatal 9L tumors engineered to secrete SF/HGF (9L-SF) and SF/HGF-negative control tumors (9L-neo) received intracardiac injections of HRP and were rapidly decapitated. Densitometric analysis of brain sections reacted with diaminobenzidine showed significantly greater extravascular HRP surrounding SF/HGF-secreting tumors than 9L-neo tumors of comparable size (p<0.05). HRP enzymatic activity associated with striata containing SF/HGF-expressing tumors was 1. 6-fold greater than that of striata containing control tumors (p<0. 05). Northern analysis showed that expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) did not differ between 9L-neo and 9L-SF tumors. These data demonstrate that SF/HGF expression by intracerebral glial tumors can enhance BTB permeability independent of changes in VEGF/VPF expression.
恶性胶质瘤与功能失调的血肿瘤屏障（BTB）相关，这会导致严重的发病率。散射因子/肝细胞生长因子（SF/HGF）是一种多功能生长因子，与胶质瘤的恶性程度相关，并且具有多种生物学特性，提示其在增强血胶质瘤屏障通透性方面发挥作用。在本研究中，我们检测了胶质瘤细胞SF/HGF表达对BTB对辣根过氧化物酶（HRP）通透性的影响。将携带经基因工程改造以分泌SF/HGF的纹状体内9L肿瘤（9L-SF）和SF/HGF阴性对照肿瘤（9L-neo）的Fischer 344大鼠进行心内注射HRP，然后迅速断头。对用二氨基联苯胺反应的脑切片进行光密度分析显示，与分泌SF/HGF的肿瘤周围相比，大小相当的9L-neo肿瘤周围的血管外HRP明显更多（p<0.05）。与含有表达SF/HGF肿瘤的纹状体相关的HRP酶活性比含有对照肿瘤的纹状体高1.6倍（p<0.05）。Northern分析显示，9L-neo和9L-SF肿瘤之间血管内皮生长因子/血管通透性因子（VEGF/VPF）的表达没有差异。这些数据表明，脑内胶质瘤细胞表达SF/HGF可独立于VEGF/VPF表达的变化增强BTB通透性。
