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Myeloid Vascular Endothelial Growth Factor Expression & its Role in Tumorigenesis

骨髓血管内皮生长因子表达

基本信息

批准号：
8210931
负责人：
RANDALL Scott JOHNSON
金额：
$ 22.29万
依托单位：
UNIVERSITY OF CAMBRIDGE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-06 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8210931
关键词：
Address Affect Angiogenic Factor Blood Vessels Bone Marrow Cell Communication Cell Survival Cells Clinic Clinical Research Cytotoxic Chemotherapy Cytotoxic agent Decision Making Development Drug Delivery Systems Endothelial Cells Epithelial Cells Excision Experimental Neoplasms Fibrosis Gene Expression Growth Growth Factor Human Hypoxia Immune Immune system Infiltration Inflammation Inflammation Process Inflammatory Inflammatory Infiltrate Inflammatory Response Injury Link Lung Malignant - descriptor Malignant Neoplasms Mammary Neoplasms Mammary Tumorigenesis Mammary gland Mediating Metastatic Lesion Modeling Molecular Molecular Profiling Mus Myelogenous Myeloid Cells Nature Neoplasm Metastasis Nutrient Oncogene Proteins Oxygen Paper Perfusion Play Polyomavirus Predisposition Process Protein Isoforms Publications Publishing Regulation Research Role Signal Transduction Solid Neoplasm Source Stem cells Sum Testing Tissues Transgenic Mice Tumor Angiogenesis VEGFA gene Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Vascularization Work Wound Healing angiogenesis cancer cell cancer therapy cell killing chemotherapy density design genetic manipulation improved macrophage malignant breast neoplasm mouse model neoplastic cell novel public health relevance recombinase research study response success therapeutic development tumor tumor growth tumor progression tumorigenesis tumorigenic

项目摘要

DESCRIPTION (provided by applicant): We have found that loss of Vascular Endothelial Growth Factor-A expression in myeloid cells has profound and unexpected effects in a mouse model of breast cancer. Our recent findings illustrate how inflammatory cells act to induce vascular changes in tumors, and how these changes alter tumor perfusion and oxygenation, as well as tumor cell survival and malignant progression. The work proposed here will allow us to explore and exploit these new and novel findings, in order to: determine the mechanisms of myeloid cell interactions with endothelial cells during tumor angiogenesis; better understand the relationship between myeloid cell VEGF expression and metastasis; and determine how these findings could be used to increase the efficacy of chemotherapy. The aims we propose to further our understanding of these phenomena are: 1: Determine the molecular mechanisms for differential VEGF signaling through innate immune cells in tumors. 2: Determine how VEGF expression from myeloid cells impacts metastasis. 3: Determine how VEGF from myeloid cells impacts chemotherapy delivery and efficacy. In sum, we believe this application will address key questions surrounding the processes of inflammation, angiogenesis, and tumor growth, with a particular emphasis on how these influence mammary tumorigenesis and metastasis. PUBLIC HEALTH RELEVANCE: These findings speak directly to breast cancer therapies currently used in the clinic, and will explore ways in which these therapies can be improved through modulation of inflammatory response.

描述（由申请人提供）：我们发现骨髓细胞中血管内皮生长因子-A表达的缺失在乳腺癌小鼠模型中具有深远和意想不到的影响。我们最近的研究结果说明了炎症细胞如何诱导肿瘤血管变化，以及这些变化如何改变肿瘤灌注和氧合，以及肿瘤细胞存活和恶性进展。本文提出的工作将使我们能够探索和利用这些新的和新颖的发现，以便：确定肿瘤血管生成过程中髓样细胞与内皮细胞相互作用的机制;更好地了解髓样细胞VEGF表达与转移之间的关系;并确定如何使用这些发现来提高化疗的疗效。我们提出进一步理解这些现象的目标是：1：确定肿瘤中通过先天免疫细胞的差异VEGF信号传导的分子机制。2：确定骨髓细胞的VEGF表达如何影响转移。3：确定来自骨髓细胞的VEGF如何影响化疗递送和疗效。总之，我们相信这一应用将解决围绕炎症，血管生成和肿瘤生长过程的关键问题，特别强调这些如何影响乳腺肿瘤发生和转移。公共卫生关系：这些发现直接说明了目前临床上使用的乳腺癌疗法，并将探索通过调节炎症反应来改善这些疗法的方法。