Role of Transient Receptor Potetial Canonical Channels in Glioma Cell Biology

描述（由申请人提供）：恶性胶质瘤被认为是胶质源性的，并且由于中位生存期低于1年，因此存在巨大的临床挑战。典型的是，它们增殖并广泛侵入整个脑实质。其他研究表明，离子通道参与神经胶质瘤细胞的增殖和迁移，最近瞬时受体电位典型（TRPC）通道家族已被牵连到其他类型的细胞，以促进增殖。因此，本研究的总体目标是了解瞬时受体电位经典通道在胶质瘤细胞生物学中的作用。具体而言，第一个目标是通过表达和电生理特征来表征神经胶质瘤细胞中的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。第二个目的是解决TRPC通道在胶质瘤细胞增殖中的作用。为了解决第二个目标，将利用各种细胞测定沿着成像技术来跟踪TRPC活性背景下的细胞周期。第三个目标是研究胶质瘤细胞如何利用TRPC通道沿着血管迁移和增殖。第三个目标将采用电生理技术，共聚焦延时显微镜和体内模型系统。公共卫生相关性：由于恶性神经胶质瘤在整个大脑中增殖和侵袭，因此确诊患者的预后极差。进一步研究神经胶质瘤用于增强增殖和侵入整个大脑的机制的研究可能会为临床治疗提供新的见解。因此，科学家，临床医生和患者将受益于这些机制的知识增加。

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.