Thompson Emily G, Sontheimer Harald
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Center for Glial Biology in Health, Disease, and Cancer, Virginia Tech Carilion Research Institute, Roanoke, VA, USA.
Eur Biophys J. 2016 Oct;45(7):635-648. doi: 10.1007/s00249-016-1154-x. Epub 2016 Jul 16.
Malignant gliomas are devastating tumors, frequently killing those diagnosed in little over a year. The profuse infiltration of glioma cells into healthy tissue surrounding the main tumor mass is one of the major obstacles limiting the improvement of patient survival. Migration along the abluminal side of blood vessels is one of the salient features of glioma cell invasion. Invading glioma cells are attracted to the vascular network, in part by the neuropeptide bradykinin, where glioma cells actively modify the gliovascular interface and undergo volumetric alterations to navigate the confined space. Critical to these volume modifications is a proposed hydrodynamic model that involves the flux of ions in and out of the cell, followed by osmotically obligated water. Ion and water channels expressed by the glioma cell are essential in this model of invasion and make opportune therapeutic targets. Lastly, there is growing evidence that vascular-associated glioma cells are able to control the vascular tone, presumably to free up space for invasion and growth. The unique mechanisms that enable perivascular glioma invasion may offer critical targets for therapeutic intervention in this devastating disease. Indeed, a chloride channel-blocking peptide has already been successfully tested in human clinical trials.
恶性胶质瘤是极具破坏性的肿瘤，常常在确诊后短短一年多的时间内就夺取患者生命。胶质瘤细胞大量浸润到主肿瘤块周围的健康组织中，这是限制患者生存率提高的主要障碍之一。沿着血管腔外侧迁移是胶质瘤细胞侵袭的显著特征之一。侵袭性胶质瘤细胞被血管网络吸引，部分原因是神经肽缓激肽，在那里胶质瘤细胞积极改变胶质瘤-血管界面并发生体积变化以在受限空间中导航。这些体积变化的关键是一种提出的流体动力学模型，该模型涉及离子进出细胞的通量，随后是渗透作用下的水。胶质瘤细胞表达的离子通道和水通道在这种侵袭模型中至关重要，并成为合适的治疗靶点。最后，越来越多的证据表明，与血管相关的胶质瘤细胞能够控制血管张力，大概是为了为侵袭和生长腾出空间。使血管周围胶质瘤侵袭成为可能的独特机制可能为这种毁灭性疾病的治疗干预提供关键靶点。事实上，一种氯离子通道阻断肽已经在人体临床试验中成功进行了测试。
