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A mu Migration Assay for Temporal Protein Localization

时间蛋白定位的 mu 迁移测定

基本信息

批准号：
7140178
负责人：
MARIBEL VAZQUEZ
金额：
$ 16.06万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2009-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Human gliomas aggressively invade the adjacent normal brain tissue to render surgical treatments for this disease impossible. Two different mouse models of glioma demonstrate two distinct patterns of migration and invasion of adjacent tissues: PDGF-induced oligodendrogliomas invade the brain as individual cells, while Ras-driven gliomas invade by tracking along blood vessels. This translational, bioengineering proposal will investigate these observations by developing and implementing a novel, nano-microfluidic assay to examine the mechanisms of brain tumor cell migration via real-time visualization of cell movement, and detection of spatial and temporal activity of signaling protein components. Our project will develop custom nanoprobes to bind, both, the extracellular and intracellular domains of the PDGF receptor in order to visualize its spatial distribution and temporal location during real-time migration in motile glioma. Further, our experiments will determine the subcellular localization of PDGFR domains relative to the direction of migration by using our microfluidic migration assay to impose controllable, one-dimensional ligand gradients onto individual cells. The proposed methodology is unique and high risk because it is the first to develop analytical tools able to measure translocations of intracellular proteins induced by a controlled, extracellular environment. Successful development of our proposed approach will enable future research to investigate cell migration via intracellular visualization of key proteins from receptors to Ras. Such ground-breaking results will elucidate unprecedented details of intracellular protein behavior during tumor cell dispersal.

描述（由申请人提供）：人类神经胶质瘤侵袭性侵入邻近的正常脑组织，使这种疾病的手术治疗成为不可能。两种不同的胶质瘤小鼠模型显示了两种不同的迁移和邻近组织侵袭模式：PDGF诱导的少突胶质细胞瘤以单个细胞侵入脑，而Ras驱动的胶质瘤通过沿沿着移动侵入。这项翻译的生物工程提案将通过开发和实施一种新型的纳米微流体检测来研究这些观察结果，以通过实时可视化细胞运动来检查脑肿瘤细胞迁移的机制，并检测信号蛋白组分的空间和时间活性。我们的项目将开发定制的纳米探针结合，无论是细胞外和细胞内的PDGF受体的结构域，以可视化其空间分布和时间位置在运动神经胶质瘤实时迁移。此外，我们的实验将确定PDGFR结构域的亚细胞定位相对于迁移的方向，通过使用我们的微流体迁移试验施加可控的，一维的配体梯度到单个细胞。所提出的方法是独特的和高风险的，因为它是第一个开发的分析工具，能够测量由受控的细胞外环境诱导的细胞内蛋白质的易位。我们提出的方法的成功开发将使未来的研究能够通过细胞内可视化从受体到Ras的关键蛋白来研究细胞迁移。这些突破性的结果将阐明肿瘤细胞扩散过程中细胞内蛋白质行为的前所未有的细节。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

EGF as a New Therapeutic Target for Medulloblastoma Metastasis.

EGF是髓母细胞瘤转移的新治疗靶标。

DOI：
10.1007/s12195-015-0395-6
发表时间：
2015-12
期刊：
Cellular and molecular bioengineering
影响因子：
2.8
作者：
Rico-Varela J;Singh T;McCutcheon S;Vazquez M
通讯作者：
Vazquez M

Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells.

DOI：
10.1007/s12195-012-0253-8
发表时间：
2012-12
期刊：
CELLULAR AND MOLECULAR BIOENGINEERING
影响因子：
2.8
作者：
Dudu, Veronica;Able, Richard A., Jr.;Rotari, Veronica;Kong, Qingjun;Vazquez, Maribel
通讯作者：
Vazquez, Maribel

Targeted extracellular nanoparticles enable intracellular detection of activated epidermal growth factor receptor in living brain cancer cells.

靶向细胞外纳米颗粒可在活脑癌细胞中对活化表皮生长因子受体的细胞内检测。