Role of Transient Receptor Potetial Canonical Channels in Glioma Cell Biology

描述(申请人提供)：恶性胶质瘤被认为是神经胶质瘤，是一个巨大的临床挑战，因为中位生存期不到1年。特征性的是，它们增殖并广泛侵入整个脑实质。其他研究表明，离子通道参与了胶质瘤细胞的增殖和迁移，最近，瞬时受体电位规范(TRPC)通道家族也被发现参与了其他类型的细胞的增殖。因此，这项研究的总体目标是了解瞬时受体电位规范通道在胶质瘤细胞生物学中所起的作用。具体地说，第一个目的是通过表达和电生理图谱来表征胶质瘤细胞中的TRPC通道。为了实现第一个目标，将利用分子和电生理技术的组合。第二个目标是解决TRPC通道在胶质瘤细胞增殖中所起的作用。为了解决第二个目标，将利用各种细胞分析和成像技术在TRPC活动的背景下跟踪细胞周期。第三个目的是研究胶质瘤细胞如何利用TRPC通道沿血管迁移和增殖。第三个目标将使用电生理学技术、共聚焦时间推移显微镜和活体模型系统。公共卫生相关性：由于恶性胶质瘤扩散并侵袭整个大脑，确诊患者的预后极差。进一步研究胶质瘤促进增殖和侵袭整个大脑的机制可能会为临床治疗的可能性提供新的见解。因此，科学家、临床医生和患者将受益于对这些机制的更多了解。

DESCRIPTION (provided by applicant): Malignant gliomas are thought to be glial-dervied and present a huge clincial challenge as the median survival is under 1 year. Characteristically, they proliferate and extensively invade throughout the brain parenchyma. Other studies have shown that ion channels are involved in the proliferation and migration of glioma cells and recently the transient receptor potential canonical (TRPC) channel family has been implicated in other cell types to facilitate proliferation. Therefore, the overall goal of this study is to understand the role transient receptor potential canonical channels play in glioma cell biology. Specifically, the first aim is to characterize TRPC channels in glioma cells by expression and electrophysiological profile. To accomplish the first aim, a combination of molecular and electrophysiological techniques will be utilized. The second aim is to address the role TRPC channels play in glioma cell proliferation. To address the second aim, a variety of cellular assays will be utilized along with imaging techniques to follow the cell cycle in the context of TRPC activity. The third aim investigates how glioma cells utilize TRPC channels in their migration and proliferation along blood vessels. The third aim will employ electrophysiological technique, confocal time-lapse microscopy, and in vivo models systems. PUBLIC HEALTH RELEVANCE: Since malignant gliomas proliferate and invade throughout the brain, the prognosis for patients diagnosed is extremely poor. Studies that further investigate the mechanisms gliomas utilize to enhance proliferation and invade throughout the brain may lend new insight into clinical treatment possibilities. Therefore, scientists, clinicians, and patients will benefit from an increased knowledge of these mechanisms.