The Role of FAK in Regulating Macrophage Migration and Function in Mammary Tumors

FAK 在调节乳腺肿瘤巨噬细胞迁移和功能中的作用

基本信息

批准号：
8893920
负责人：
Ryan Llewellyn
金额：
$ 2.98万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8893920
关键词：
Acrylamides Address Adhesions Adopted Alleles Automobile Driving Blood Circulation Blood Vessels Bone Marrow Breast Cancer Model Breast Cancer Treatment Cancer Patient Cell Lineage Cell physiology Cell-Cell Adhesion Cells Chemotaxis Clinical Cues Data Deposition Development Elements Environment Exhibits Extracellular Matrix Extravasation Fibrosis Focal Adhesion Kinase 1 Foundations Genotype Growth Factor Hallmark Cell Health Hypoxia ITGAM gene Immunoglobulin Variable Region Immunohistochemistry In Vitro Infiltration Inflammatory Influentials Integrins Knock-out Laboratories Malignant Neoplasms Mammary Neoplasms Measures Mediator of activation protein Molecular Mouse Mammary Tumor Virus Movement Mus Myelogenous Necrosis Neoplasm Metastasis Outcome Patients Phagocytosis Phenotype Play Primary Neoplasm Process Production Proteins Recruitment Activity Research Research Personnel Research Training Role Signal Transduction Staging Testing Tissues To specify Training Tumor Burden base career cell motility cell type crosslink cytokine functional plasticity in vitro testing insight macrophage malignant breast neoplasm meetings migration monocyte prevent symposium treatment strategy tumor tumor growth tumor microenvironment tumor progression

项目摘要

DESCRIPTION (provided by applicant): There is considerable evidence that non-transformed elements of the tumor microenvironment can play a substantial role in breast cancer progression and patient outcome. Cells of the monocyte/macrophage lineage comprise a significant portion of the breast tumor stroma, and are influential throughout the development of the tumor. A hallmark of these cells is their functional plasticity, which contributes to the fact hat tumor-associated macrophages (TAMs) have been shown to both support and inhibit tumor growth and metastasis. Adhesion signaling is used by macrophages for a variety of cellular functions, including chemotaxis, extravasation from blood vessels, and phagocytosis. The research component of this proposal will address the fundamental contribution of Focal Adhesion Kinase (FAK), a critical mediator of adhesion signaling and motility, to macrophage functions regulating primary breast tumor outgrowth. We will test the hypotheses that FAK plays a crucial role in facilitating migration of TAMs from the tumor vasculature to specified microdomains within the tumor microenvironment (Aim 1) and/or controls functions in macrophages that contribute to breast tumor control and progression (Aim 2). This research will provide new insights into the mechanisms driving breast tumor growth and raise new considerations for breast cancer treatments. The research component of this proposal will be supplemented with an active training plan that includes: (1) didactic coursework and training, (2) participation in research meetings and seminars, and (3) participation in scientific conferences. Together, the research and training plans will provide a strong foundation upon which to build a career as a successful, independent breast cancer researcher.

描述（由申请人提供）：有大量证据表明肿瘤微环境的非转化元素可以在乳腺癌进展和患者结果中发挥重要作用。单核细胞/巨噬细胞谱系的细胞构成乳腺肿瘤基质的重要部分，并且在整个肿瘤的发展过程中都有影响。这些细胞的一个标志是它们的功能可塑性，这使得肿瘤相关巨噬细胞（TAM）已被证明可以支持和抑制肿瘤生长和转移。巨噬细胞利用粘附信号传导来实现多种细胞功能，包括趋化性、血管外渗和吞噬作用。该提案的研究部分将解决粘着斑激酶（FAK）的基本贡献，FAK是粘着信号和运动的关键介质，对调节原发性乳腺肿瘤生长的巨噬细胞功能。我们将测试以下假设：FAK 在促进 TAM 从肿瘤脉管系统迁移到肿瘤微环境内的特定微域（目标 1）和/或控制巨噬细胞中有助于乳腺肿瘤控制和进展的功能方面发挥着至关重要的作用（目标 2）。这项研究将为乳腺肿瘤生长的驱动机制提供新的见解，并为乳腺癌治疗提出新的考虑。该提案的研究部分将辅以积极的培训计划，其中包括：（1）教学课程和培训，（2）参加研究会议和研讨会，以及（3）参加科学会议。这些研究和培训计划将为成为一名成功的独立乳腺癌研究人员奠定坚实的基础。