Lee Jisook, Lund-Smith Caren, Borboa Alexandra, Gonzalez Ana M, Baird Andrew, Eliceiri Brian P
Department of Surgery, Division of Trauma, 212 Dickinson Street, San Diego, CA 92103, USA.
Brain Res. 2009 Sep 8;1288:125-34. doi: 10.1016/j.brainres.2009.06.095. Epub 2009 Jul 9.
The normal BBB (blood-brain barrier) consists of a series of structures collectively known as neurovascular units, or NVU, that are composed of endothelial cells and astrocyte endfeet separated by a basal lamina at their interface. The integrity of the BBB and specifically endothelial tight junctions is maintained by interactions between these different components and the local microenvironment of the NVU. Central nervous system cancers such as gliomas disrupt the integrity of the BBB and this compromise is associated with increased tumor growth and invasion of the surrounding brain parenchyma. Because the relationship between glioma-induced BBB breakdown and glioma invasion remains poorly understood, and the host microenvironment can influence tumor cell migration, we used immunohistochemical techniques to characterize tumor associated BBB remodeling. Using an orthotopic xenograft model of glioma, we demonstrate that tumor cells induce specific changes in the composition of the basal lamina and in astrocytic components of the NVU. We suggest that these changes may be essential to understand the capacity of gliomas to regulate BBB integrity and as such, glioma invasion into brain parenchyma.
正常的血脑屏障（BBB）由一系列统称为神经血管单元（NVU）的结构组成，这些结构由内皮细胞和星形胶质细胞终足组成，它们在界面处被基膜分隔。血脑屏障的完整性，特别是内皮紧密连接，是由这些不同成分与神经血管单元的局部微环境之间的相互作用维持的。中枢神经系统癌症，如神经胶质瘤，会破坏血脑屏障的完整性，而这种损害与肿瘤生长增加和周围脑实质的侵袭有关。由于神经胶质瘤诱导的血脑屏障破坏与神经胶质瘤侵袭之间的关系仍知之甚少，并且宿主微环境可影响肿瘤细胞迁移，因此我们使用免疫组织化学技术来表征肿瘤相关的血脑屏障重塑。使用神经胶质瘤的原位异种移植模型，我们证明肿瘤细胞会诱导基膜成分和神经血管单元的星形胶质细胞成分发生特定变化。我们认为，这些变化对于理解神经胶质瘤调节血脑屏障完整性的能力以及神经胶质瘤侵袭脑实质的能力可能至关重要。
