(PQA2) MAMMALIAN REGENERATION, HIGH FAT DIETS, AND BREAST CANCER: A COMMON LINK?

(PQA2) 哺乳动物再生、高脂肪饮食和乳腺癌：共同的联系？

基本信息

批准号：
9086307
负责人：
Ellen s. Heber-Katz
金额：
$ 33.91万
依托单位：
LANKENAU INSTITUTE FOR MEDICAL RESEARCH
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：
2013-08-16 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9086307
关键词：
4T1 Ablation Address Adipocytes Adult Autoimmunity Biological Assay Breast Cancer Cell Breast Cancer Model Candidate Disease Gene Cell Communication Cell Proliferation Cells Chromosome Mapping Chronic Coculture Techniques Complex Endothelial Cells Environment Etiology FABP4 gene Fat-Restricted Diet Fatty acid glycerol esters Female Genes Genetic study Goals Growth Health High Fat Diet Human Immune response Immunocompetent In Vitro Inbred BALB C Mice Inflammation Inflammatory Injection of therapeutic agent LG/J Mouse Laboratories Lead Link MRL/MpJ Mouse Malignant Neoplasms Mammary Neoplasms Measures Modeling Molecular Mouse Strains Mus Natural regeneration Neoplasm Metastasis Newts Obesity Oils PECAM1 gene PTPRC gene Parents Phenotype Population Predisposition Primary Neoplasm Regulation Resolution Role Site Stromal Cells Study Subject System Therapeutic Tissues Tumor Immunity Tumor-Derived Vascularization Work Wound Healing angiogenesis base blastema cancer cell cancer therapy cell growth diet and cancer feeding fibroblast-activating factor genetic signature implantation in vivo inflammatory marker innovation insight knock-down malignant breast neoplasm mouse model neoplastic cell novel rapid growth regenerative response three dimensional cell culture tumor tumor growth tumor microenvironment tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Obesity, often the result of a high fat diet, leads to chronic inflammation and stromal cell proliferation. In this application, we will address the issue of how a high fat diet leads to enhanced tumor cell growth and approach this from a previously unexplored direction. Examination of an adult mammalian regeneration model employing the MRL/MpJ mouse studied for its susceptibility to autoimmunity, obesity, and enhanced wound healing abilities, displays multiple phenotypes similar to the tumor microenvironment and has been the subject of study in the Heber-Katz laboratory for over a decade. The mapping of genes in this mouse has led to the identification of a novel gene signature defined by a small subset of genes which are regulated by a high fat diet in a sexually dimorphic fashion. The genes that constitute this so-called "high fat-selected regeneration-associated" or HFSRA gene signature are the basis of the proposed approach to defining the mechanistic basis for the association between a high fat diet and breast cancer. This approach is strongly supported by results demonstrating that these same genes are similarly expressed in human breast cancer-derived stromal cells. These studies will utilize the 4T1 orthotopic mouse breast cancer model in syngeneic BALB/c mice in vivo. In vitro studies will be carried out using 3D-culture systems relevant to the tumor microenvironment based on an understanding of the complexities of the tumor microenvironment and the host response to tumors, ranging from the role of stromal cells, inflammation and vascularization to tumor immunity, and is the focus of the Pur� laboratory. Working together as a team, the combined expertise of Drs. Heber-Katz and Pur� render the important but complex goals of this project eminently feasible.

描述（由应用提供）：肥胖通常是高脂饮食的结果，导致慢性感染和基质细胞增殖。在此应用程序中，我们将解决这个问题关于高脂肪饮食如何导致肿瘤细胞生长增强，并从以前出乎意料的方向接近这一点。检查采用MRL/MPJ小鼠Studiod的成年哺乳动物再生模型的检查，以易于自身免疫性，肥胖和增强的伤口愈合能力，显示出与肿瘤微环境相似的多种表型，并且在十年来一直是Heber-Katz实验室中的研究主题。该小鼠中基因的映射导致鉴定了由一小部分基因定义的新型基因特征，这些基因以性二态性方式受到高脂饮食的调节。构成这种所谓的“高脂肪选择的再生相关”或HFSRA基因特征的基因是提出方法定义高脂肪饮食与乳腺癌之间关联的机械基础的基础。结果表明，这些相同基因在人类乳腺癌衍生的基质细胞中类似表达的结果得到了强烈支持。这些研究将利用体内的合成性BALB/C小鼠中的4T1原位小鼠乳腺癌模型。基于对肿瘤微环境的复杂性以及对肿瘤的宿主反应的理解，将使用与肿瘤微环境相关的3D培养系统进行体外研究，从基质细胞，感染和血管化的作用，肿瘤免疫学到肿瘤的作用，并且是PUR实验室的焦点。作为团队合作，DR的综合专业知识。 Heber-Katz和Pur'使该项目的重要但复杂的目标非常可行。