Arosarena O, Guerin C, Brem H, Laterra J
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Brain Res. 1994 Mar 21;640(1-2):98-104. doi: 10.1016/0006-8993(94)91861-9.
Blood-brain barrier (BBB) properties of endothelial cells have on impact on brain tumor behavior, diagnosis, and response to therapy. Biochemical BBB properties are expressed by endothelial cells within intracerebral (IC) gliomas but little is known regarding the expression of BBB-associated proteins within gliomas established subcutaneously (SC), a site that is frequently used in experimental glioma models. We compared the expression of two BBB proteins, glucose transporter type-1 (Glut1) and endothelial barrier antigen (EBA), in IC and SC rat 9L and F98 gliomas. The percentage of microvessels with immunohistochemically-detectable Glut1 and EBA in IC 9L tumors (31-98%) contrasted with that found in SC 9L tumors (0-3.9%) (P < 0.0001). Likewise, the percentage of immunohistochemically-positive vessels in IC F98 tumors (35-66%) differed markedly from that in SC F98 tumors (0%) (P < 0.0001). These differences were not explained by effects of tumor location on vessel density or tumor histology. These findings demonstrate that the peritumoral environment influences endothelial differentiation within glial tumors and suggest that glioma cells maintain but do not induce the expression of barrier properties in vessels that infiltrate tumor from surrounding tissue.
内皮细胞的血脑屏障（BBB）特性对脑肿瘤的行为、诊断及治疗反应均有影响。脑内（IC）胶质瘤内的内皮细胞可表达血脑屏障的生化特性，但对于皮下（SC）接种的胶质瘤（实验性胶质瘤模型中常用的位点）内血脑屏障相关蛋白的表达情况却知之甚少。我们比较了IC和SC大鼠9L及F98胶质瘤中两种血脑屏障蛋白，即葡萄糖转运蛋白1型（Glut1）和内皮屏障抗原（EBA）的表达情况。IC 9L肿瘤中免疫组化可检测到Glut1和EBA的微血管百分比为31% - 98%，而SC 9L肿瘤中的该百分比为0% - 3.9%（P < 0.0001）。同样，IC F98肿瘤中免疫组化阳性血管的百分比为35% - 66%，与SC F98肿瘤中的0%显著不同（P < 0.0001）。肿瘤位置对血管密度或肿瘤组织学的影响并不能解释这些差异。这些发现表明肿瘤周围环境会影响胶质肿瘤内的内皮细胞分化，并提示胶质瘤细胞维持但不诱导从周围组织浸润肿瘤的血管中屏障特性的表达。
