Leukotriene-Induced Nestin Expression Promotes Medulloblastoma Tumorigenesis

描述（申请人提供）：髓母细胞瘤（Medulloblastoma， MB）是儿童最常见的恶性脑肿瘤。它的快速生长和通过神经系统扩散的趋势需要使用极端积极和有毒的治疗方法。即使采用这种治疗方法，仍有很大比例的患者死于这种疾病，幸存者往往遭受严重的长期副作用，如认知缺陷和内分泌紊乱。迫切需要改进治疗MB的策略。本研究的目的是探索MB的靶向治疗方法。初步研究表明，细胞骨架蛋白Nestin对MB细胞增殖至关重要。在本研究中，研究者将进一步确定Nestin促进MB发展的机制。此外，最近的研究表明，肿瘤细胞中Nestin的表达需要一种脂质介质白三烯，抑制白三烯的合成可显著抑制肿瘤细胞的增殖。因此，本研究提出检测白三烯抑制剂治疗小鼠MBs的治疗潜力。这些研究将显著加深我们对MB发生的分子基础的认识，并为白三烯抑制剂在治疗人MB中的应用铺平道路。

DESCRIPTION (provided by applicant): Medulloblastoma (MB) is the most common malignant brain tumor in children. Its rapid growth and tendency to spread through the nervous system necessitate the use of extreme aggressive and toxic therapies. Even with such therapies, a significant proportion of patients die from this disease, and survivors often suffer severe long-term side effects such as cognitive deficits and endocrine disorders. Improved strategies for treating MB are urgently needed. The goal of this study is to explore the targeted therapeutic approaches for MB. Preliminary studies suggest that a cytoskeletal protein, Nestin is essential for MB cell proliferation. In this proposal, investigators will further determine the mechanisms for Nestin in promoting MB development. In addition, recent studies have revealed that leukotriene, a lipid mediator, is required for Nestin expression in tumor cells and inhibitionof leukotriene synthesis significantly prevents tumor cell proliferation. This study therefore proposes to examine the therapeutic potentials of leukotriene inhibitors in treating MBs in mice. These studies would significantly deepen our understanding of the molecular basis for MB development, and pave the road for the application of leukotriene inhibitors in treating human MB.