(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：
8590786
负责人：
Ellen s. Heber-Katz
金额：
$ 37.75万
依托单位：
WISTAR INSTITUTE
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 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8590786
关键词：
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 Diet Endothelial Cells Environment Etiology FABP4 gene Fat-Restricted Diet Fatty acid glycerol esters Female Genes Genetic Goals Growth 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 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 implantation in vivo inflammatory marker innovation insight malignant breast neoplasm mouse model neoplastic cell novel oil red O public health relevance rapid growth regenerative response 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（由申请人提供）：肥胖通常是高脂肪饮食的结果，会导致慢性炎症和基质细胞增殖。在本申请中，我们将解决这个问题。研究人员利用 MRL/MpJ 小鼠对成年哺乳动物再生模型进行了研究，研究了高脂肪饮食如何导致肿瘤细胞生长增强，并从先前未探索的方向研究了其对自身免疫、肥胖和增强伤口愈合能力的易感性。与肿瘤微环境相似的多种表型，十多年来一直是 Heber-Katz 实验室的研究主题。该小鼠的基因图谱鉴定了由一小部分基因定义的新基因特征。构成这种所谓的“高脂肪选择再生相关”或 HFSRA 基因特征的基因是所提出的定义机制基础的方法的基础。高脂肪饮食与乳腺癌之间的关联得到了结果的有力支持，这些结果表明这些相同的基因在人类乳腺癌衍生的基质细胞中表达相似，这些研究将在同基因中利用 4T1 原位小鼠乳腺癌模型。 BALB/c 小鼠体内研究将使用与肿瘤微环境相关的 3D 培养系统进行，该系统基于对肿瘤微环境的复杂性和宿主对肿瘤的反应的了解，包括基质细胞的作用、炎症和血管化对肿瘤免疫的影响，是 Pur¿实验室合作，Heber-Katz 博士和 Pur¿使该项目的重要但复杂的目标变得非常可行。