Staflin Karin, Lindvall Magnus, Zuchner Thole, Lundberg Cecilia
Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
J Neurosci Res. 2007 Aug 1;85(10):2147-59. doi: 10.1002/jnr.21344.
Gliomas are the most common primary brain tumors and offer a poor prognosis in patients because of their infiltrative and treatment-resistant nature. The median survival time after diagnosis is approximately 11-12 months. There is a strong need for novel treatment modalities in targeting gliomas, and recent advances use neural progenitor cells as delivery systems for different therapeutic strategies. In this study, we show that rat embryonic neural progenitor cell (NPC) lines, transplanted at a distant site from a 3-day-preestablished glioma in the striatum, were able to migrate toward and colocalize with tumor isles without general spread into the brain parenchyma. Upon encounter with tumor, neural progenitor cells changed phenotype and became vimentin positive. These results demonstrate that transplanted neural progenitor cells respond to queues from a tumor and home to and exert an antitumor effect on the preestablished glioma, significantly decreasing the tumor volume with approximately 67% compared with control tumors after 1-2 weeks. Moreover, these early effects could be translated into increased survival times of animals treated with neural progenitor cell grafts 3 days after intrastriatal tumor inoculation. In contrast, there was no activation or migration of endogenous subventricular zone (SVZ) neuroblasts in response to an intrastriatal syngeneic tumor. In conclusion, NPC possess the ability to influence tumor growth as well as respond to queues from the tumor or tumor microenvironment, demonstrating a cross-talk between the cells.
神经胶质瘤是最常见的原发性脑肿瘤，由于其浸润性和抗治疗性，患者预后较差。诊断后的中位生存时间约为11 - 12个月。迫切需要针对神经胶质瘤的新型治疗方法，最近的进展是将神经祖细胞用作不同治疗策略的递送系统。在本研究中，我们表明，大鼠胚胎神经祖细胞（NPC）系移植到纹状体中预先建立3天的神经胶质瘤远处部位后，能够向肿瘤岛迁移并与其共定位，而不会广泛扩散到脑实质中。遇到肿瘤后，神经祖细胞改变表型，波形蛋白呈阳性。这些结果表明，移植的神经祖细胞对肿瘤发出的信号做出反应，归巢到预先建立的神经胶质瘤并对其发挥抗肿瘤作用，与对照肿瘤相比，1 - 2周后肿瘤体积显著减小约67%。此外，这些早期效应可转化为纹状体内接种肿瘤3天后接受神经祖细胞移植治疗的动物生存时间延长。相比之下，纹状体内同基因肿瘤并未引发内源性脑室下区（SVZ）神经母细胞的激活或迁移。总之，NPC具有影响肿瘤生长以及对肿瘤或肿瘤微环境发出的信号做出反应的能力，表明细胞之间存在相互作用。
