Interleukin-4 Drives Tumor-Associated Macrophage Polarization to Promote Tumor Gr

Interleukin-4驱动肿瘤相关巨噬细胞极化促进肿瘤生长

• 批准号: 8751741
• 负责人: Steven Allen
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-14 至 2016-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8751741
• 关键词: Area; Automobile Driving; Breast; Cause of Death; Cell Line; Cell Nucleus; Characteristics; Coupled; Diagnosis; Environment; Fostering; Future; Goals; Growth; Immune response; Immunity; Inflammation; Inflammatory; Interleukin 4 Receptor; Interleukin-4; Knockout Mice; Knowledge; Lead; Life; Malignant Neoplasms; Mediating; Methods; Mission; Modeling; Mus; NF-kappa B; Neoplasm Metastasis; Neoplasms in Vascular Tissue; Nuclear; Nuclear Translocation; Observational Study; Pathway interactions; Patients; Phenotype; Play; Primary Neoplasm; Public Health; Research; Research Personnel; Role; STAT6 Transcription Factor; Scientist; Signal Transduction; Source; Stimulus; T-Lymphocyte; TNFRSF5 gene; Tissues; Tumor Cell Invasion; Tumor Cell Line; United States; United States National Institutes of Health; allergic response; angiogenesis; burden of illness; cancer therapy; cell type; cytokine; in vivo; macrophage; malignant breast neoplasm; microbicide; migration; outcome forecast; overexpression; p65; prevent; public health relevance; response; tumor; tumor growth; tumor microenvironment; tumor progression

DESCRIPTION (provided by applicant): Despite many advances in the battle against cancer, it remains a dreaded diagnosis and a leading cause of death in the United States. The rationale and hope for this proposed research is that any and all knowledge gained in understating how cancer progresses and infiltrates areas of the body brings, not only scientists, but the patients and public closer to achieving their common goal of complete eradication of cancers. The environment surrounding tumors is known to be one of smoldering inflammation and one cell type, known as a tumor-associated macrophage (TAM), prevalent in this environment has been shown to promote many aspects of cancer. TAMs foster tumor progression in multiple ways; they support new tumor blood vessel growth, tumor cell invasion, and even enhance metastasis. A key objective of this proposal is to understand the origin of the cellular signals that stimulate TAM's pro-tumor functions and how these signals act on TAMs. The proposed research is relevant to public health because understanding all of the sources and factors that influence cancer growth and metastasis - be they from the tumor or the body - will ultimately lead to discoveries of how to prevent tumors. Thus, this research is directly relevant to the NIH mission to seek fundamental knowledge that will reduce the burden of illness and lengthen life. The methods employed in order to achieve this goal will be to study tumor models in mice. Tumors will be generated that either do or do not secrete a certain signal, interleukin-4 (IL-4), and then these tumors investigated in mice that either do or do not have the ability to produce IL-4. Also, IL-4 and its effects on TAMs both with and without the IL-4 receptor will be studied to help discern how it might play a role in promoting cancer. The specific aims of this project are to determine the effects of IL-4 secreted from the tumor on tumor growth, metastasis, and TAMs and to understand how IL-4 signals to TAMs to achieve its pro- cancer consequences. It is expected that the impact of the results of this study will be in allowing researchers to target TAMs with future anti-cancer therapy from multiple avenues.

描述（由申请人提供）：尽管在与癌症的斗争中取得了许多进展，但它仍然是一个可怕的诊断和美国的主要死因。这项拟议研究的理由和希望是，在了解癌症如何进展和身体浸润区域方面获得的任何和所有知识不仅使科学家，而且使患者和公众更接近实现完全根除癌症的共同目标。 已知肿瘤周围的环境是阴燃性炎症之一，并且在这种环境中普遍存在的一种称为肿瘤相关巨噬细胞（TAM）的细胞类型已被证明促进癌症的许多方面。TAM以多种方式促进肿瘤进展;它们支持新的肿瘤血管生长，肿瘤细胞侵袭，甚至增强转移。该提案的一个关键目标是了解刺激细胞信号的起源。 TAM的促肿瘤功能以及这些信号如何作用于TAM。 这项拟议中的研究与公共卫生有关，因为了解影响癌症生长和转移的所有来源和因素-无论是来自肿瘤还是身体-最终将导致发现如何预防肿瘤。因此，这项研究与NIH的使命直接相关，即寻求减少疾病负担和延长寿命的基础知识。 为了实现这一目标所采用的方法将是研究小鼠肿瘤模型。肿瘤会产生，要么分泌或不分泌某种信号，白细胞介素-4（IL-4），然后 这些肿瘤在具有或不具有产生IL-4能力的小鼠中进行研究。此外，将研究IL-4及其对有和没有IL-4受体的TAM的影响，以帮助辨别它如何在促进癌症中发挥作用。 该项目的具体目的是确定从肿瘤分泌的IL-4对肿瘤生长、转移和TAM的影响，并了解IL-4如何向TAM发出信号以实现其促癌后果。预计这项研究结果的影响将使研究人员能够通过多种途径在未来的抗癌治疗中靶向TAM。