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

• 批准号: 7720544
• 负责人: CHARLOTTE M VINES
• 金额: $ 17.1万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/7720544
• 关键词: Aspirin; Behavior; Breast; CC chemokine receptor 7; CCL19 gene; CCL21 gene; Cell Line; Cells; Computer Retrieval of Information on Scientific Projects Database; Development; Epithelium; FVB Mouse; Funding; Grant; Injection of therapeutic agent; Institution; Ligands; Lung; Measures; Modeling; Mus; Neoplasm Metastasis; Pain; Protein Overexpression; Research; Research Personnel; Resources; Role; Signal Transduction; Site; Source; T-Cell Development; T-Lymphocyte; Tetracycline; Tetracyclines; Transcriptional Activation; United States National Institutes of Health; Up-Regulation; Work; beta-Chemokines; cell motility; chemokine receptor; day; expression vector; in vivo Model; lymph nodes; malignant breast neoplasm; migration; mouse model; neoplastic cell; prophylactic; thymocyte; trafficking; tumor; vector

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 C-C 趋化因子受体 7 (CCR7) 调节 na¿为了开发体内模型来了解控制细胞迁移的 CCR7 信号传导，我们开发了一种转移模型，该模型通常也表达于 T 细胞发育过程中。乳腺上皮细胞中的低水平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 CCR7 在转移中的作用，我们开发了两种小鼠模型。为了了解发育过程中 CCR7 的早期表达是否可以阻止肿瘤转移，我们生成了一种四环素可调节的 CCR7 表达载体，该载体在 N 末端融合到 myc。该载体将用于与 C57/Bl6 同源的两种细胞系。小鼠；高转移性 4T07 和非转移性 67NR 细胞系，以确定 CCR7 是否可以改变具有转移性的细胞系的迁移效率或靶向。由于可预测的转移行为，我们在 PyVMT 细胞中过度表达了组成型激活的 CCR7，据报道，PyVMT 细胞与 FVB 小鼠是同源的。根据我们 LAR 设施的要求，所有小鼠都接受了阿司匹林作为预防措施。尽管小鼠被注射了 5 x105 个肿瘤细胞，但这些小鼠模型的特征是仅在 28 天内形成肿瘤。 137 只注射小鼠中有 8 只在一年内在注射部位出现了肿瘤。肿瘤的发生与 CCR7 的表达无关。