Sontheimer Harald
Department of Neurobiology and Civitan International Research Center, the University of Alabama at Birmingham, Birmingham, AL, USA.
Mol Neurobiol. 2004 Feb;29(1):61-71. doi: 10.1385/MN:29:1:61.
The malignant growth of glial support cells causes gliomas, highly invasive, primary brain tumors that are largely resistant to therapy. Individual tumor cells spread by active cell migration, invading diffusely into the normal brain. This process is facilitated by Cl- channels that endow glioma cells with an enhanced ability to quickly adjust their shape and cell volume to fit the narrow and tortuous extracellular brain spaces. Once satellite tumors enlarge, their growth is limited by the spatial constraints imposed by the bony cavity of the skull and spinal column. Glioma cells circumvent this limitation by active destruction of peritumoral neural tissue through the release of glutamate, inducing peritumoral seizures and ultimately excitotoxic neuronal cell death. Hence, primary brain tumors support their unusual biology by taking advantage of ion channels and transporters that are designed to support ion homeostatic functions in normal brain.
神经胶质支持细胞的恶性生长会导致胶质瘤，这是一种具有高度侵袭性的原发性脑肿瘤，对治疗大多具有抗性。单个肿瘤细胞通过活跃的细胞迁移进行扩散，弥漫性地侵入正常脑组织。氯离子通道促进了这一过程，这些通道赋予胶质瘤细胞更强的能力，使其能够快速调整自身形状和细胞体积，以适应狭窄且曲折的细胞外脑间隙。一旦卫星肿瘤增大，其生长就会受到颅骨和脊柱骨腔所施加的空间限制。胶质瘤细胞通过释放谷氨酸来主动破坏瘤周神经组织，从而规避这一限制，引发瘤周癫痫发作并最终导致兴奋性毒性神经元细胞死亡。因此，原发性脑肿瘤通过利用那些旨在维持正常脑内离子稳态功能的离子通道和转运体来支持其异常生物学特性。
