Leukotriene-Induced Nestin Expression Promotes Medulloblastoma Tumorigenesis

点击翻译按钮获取中文摘要

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.