DIFFERENTIAL SIGNALING OF CCR7 THROUGH ITS 2 ENDOGENOUS LIGANDS, CCL19 & CCL21

CCR7 通过其 2 个内源配体 CCL19 的差异信号传导

基本信息

  • 批准号:
    7720544
  • 负责人:
  • 金额:
    $ 17.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-07-01 至 2009-06-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The C-C chemokine receptor 7 (CCR7) regulates trafficking of na¿ve thymocytes during T cell development and during localization of T cells to and within lymph nodes. To develop an in vivo model to understand the signaling of CCR7 that controls migration of cells, we developed a metasis model. CCR7, which is also normally expressed at low levels in breast epithelia is up-regulated in certain breast cancers, however, the role of this up-regulation in tumor development/metastasis remains unclear. To define the role for CCR7 in metastasis we worked to develop two mouse models. To understand whether early expression of CCR7 during tumor development could block tumor metastasis, we generated a tetracycline regulatable CCR7 expression vector that was fused at the N-terminus to myc. This vector was to be used in two cell lines that are syngeneic with C57/Bl6 mice; the highly metastatic 4T07 and as a the non-metastatic 67NR cell lines. To determine if CCR7 could change the migration efficiency or targeting of a line that had a predictable metastatic behavior, we overexpressed constitutively activated CCR7 in the the PyVMT cells that reportedly migrate only to the lungs. PyVMT cells are syngeneic with FVB mice. Following a request by our LAR facility, all mice were pre-treated with aspirin, as a prophylactic measure for pain, prior to tumor injections. Although the mice were injected with 5 x105 tumor cells, and these mouse models characteristically develop tumors within 28 days only 8 of the 137 injected mice developed tumors at the injection site over a one year period. The development of tumors did not correlate with expression of CCR7.
这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者(PI)可能从另一个NIH来源获得了主要资金, 因此可以在其他CRISP条目中表示。所列机构为 研究中心,而研究中心不一定是研究者所在的机构。 C-C趋化因子受体7(CCR 7)在T细胞发育期间和T细胞定位于淋巴结和淋巴结内期间调节幼稚胸腺细胞的运输。为了开发体内模型以理解控制细胞迁移的CCR 7的信号传导,我们开发了转移模型。 CCR 7通常在乳腺上皮中也以低水平表达,在某些乳腺癌中上调,然而,这种上调在肿瘤发展/转移中的作用仍不清楚。 为了确定CCR 7在转移中的作用,我们开发了两种小鼠模型。 为了了解在肿瘤发展过程中CCR 7的早期表达是否可以阻断肿瘤转移,我们产生了四环素可调节的CCR 7表达载体,其在N-末端融合到myc。 该载体将用于与C57/B16小鼠同基因的两种细胞系;高转移性4 T07和非转移性67 NR细胞系。 为了确定CCR 7是否可以改变具有可预测的转移行为的细胞系的迁移效率或靶向,我们在PyVMT细胞中过表达组成型激活的CCR 7,据报道该细胞仅迁移到肺。 PyVMT细胞与FVB小鼠同基因。根据我们LAR机构的要求,在肿瘤注射之前,所有小鼠均用阿司匹林预处理,作为疼痛的预防措施。尽管小鼠注射了5 × 105个肿瘤细胞,并且这些小鼠模型在28天内典型地发展肿瘤,但在一年的时间内,137只注射小鼠中只有8只在注射部位发展肿瘤。 肿瘤的发生与CCR 7的表达无关。

项目成果

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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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CHARLOTTE M VINES其他文献

CHARLOTTE M VINES的其他文献

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{{ truncateString('CHARLOTTE M VINES', 18)}}的其他基金

Development of a Mouse Model to Study Targeted Therapy to Prevent CNS Invasion by Pediatric T-ALL
开发小鼠模型来研究预防儿童 T-ALL 侵袭中枢神经系统的靶向治疗
  • 批准号:
    10579626
  • 财政年份:
    2022
  • 资助金额:
    $ 17.1万
  • 项目类别:
CCL19 Regulation of the Secondary Immune Response
CCL19 二次免疫反应的调节
  • 批准号:
    9096831
  • 财政年份:
    2015
  • 资助金额:
    $ 17.1万
  • 项目类别:
CCR7 Chemotaxis Regulates Memory T Cell Localization
CCR7 趋化性调节记忆 T 细胞定位
  • 批准号:
    10341145
  • 财政年份:
    2015
  • 资助金额:
    $ 17.1万
  • 项目类别:
CCR7 Chemotaxis Regulates Memory T Cell Localization
CCR7 趋化性调节记忆 T 细胞定位
  • 批准号:
    10546442
  • 财政年份:
    2015
  • 资助金额:
    $ 17.1万
  • 项目类别:
REGULATION OF CCR7 MEDIATED EVENTS IN BREAST CANCER CELLS AND IN T CELLS
乳腺癌细胞和 T 细胞中 CCR7 介导的事件的调节
  • 批准号:
    8168395
  • 财政年份:
    2010
  • 资助金额:
    $ 17.1万
  • 项目类别:
CCR7 REGULATION OF ERK5 PHOSPHORYLATION DURING AN IMMUNE RESPONSE
免疫反应期间 CCR7 对 ERK5 磷酸化的调节
  • 批准号:
    7959691
  • 财政年份:
    2009
  • 资助金额:
    $ 17.1万
  • 项目类别:
CCR7 REGULATION OF IMMUNE AND NON-IMMUNE CELL ADHESION/MIGRATION
CCR7 对免疫和非免疫细胞粘附/迁移的调节
  • 批准号:
    7609894
  • 财政年份:
    2007
  • 资助金额:
    $ 17.1万
  • 项目类别:
REGULATION OF CCR7 MEDIATED ADHESION OF T CELLS THROUGH LFA-1
通过 LFA-1 调节 CCR7 介导的 T 细胞粘附
  • 批准号:
    7381287
  • 财政年份:
    2006
  • 资助金额:
    $ 17.1万
  • 项目类别:
The Role of Arrestins in CCR7 Trafficking
逮捕令在 CCR7 贩运中的作用
  • 批准号:
    6809620
  • 财政年份:
    2005
  • 资助金额:
    $ 17.1万
  • 项目类别:
REGULATION OF CCR7 DURING ?2 INTEGRIN-MEDIATED ADHESION
?2 整合素介导的粘附过程中 CCR7 的调节
  • 批准号:
    7170530
  • 财政年份:
    2005
  • 资助金额:
    $ 17.1万
  • 项目类别:

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