Impact of Cellular and Extracellular Host Components on Tumor Progression

细胞和细胞外宿主成分对肿瘤进展的影响

基本信息

批准号：
8906800
负责人：
RICHARD O HYNES
金额：
$ 72.9万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
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：
2011-09-23 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8906800
关键词：
Address Adhesions Affect Aggressive behavior Area Behavior Binding Biochemical Biological Biological Markers Biology Biopsy Blood Circulation Bone Marrow Bone Marrow Cells Breast Cancer Model Cancer Model Cell model Cell physiology Cells Cellular biology Chest Clinical Clinical Data Collaborations Collection Complex Data Development Diagnostic Distant Doctor of Philosophy Endocrine Epithelial Etiology Exhibits Extracellular Matrix Extracellular Matrix Proteins Extramedullary Extravasation Fibroblasts Funding General Hospitals Generations Genes Genetically Engineered Mouse Goals Growth Factor Hematopoietic Human Individual Inflammatory Institutes Instruction Integrins Invaded Investigation Laboratories Link Lung Adenocarcinoma Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of lung Mass Spectrum Analysis Massachusetts Medicine Mesenchymal Methods Modeling Molecular Mus Myeloid Cells Myofibroblast Nature Neoplasm Metastasis Neoplastic Epithelial Cell Neoplastic Stromal Cell Non-Small-Cell Lung Carcinoma Normal Cell Oncologist Organ Paracrine Communication Pathogenesis Patients Phenotype Physiological Play Primary Neoplasm Process Prognostic Marker Property Proteins Proteomics Reagent Recording of previous events Recruitment Activity Research Research Project Grants Role Sampling Signal Transduction Site Spleen Splenomegaly Stem cells Stromal Cells System Systems Biology Tenascin Testing Therapeutic Intervention Tissue Microarray Tissue Sample Tissues Tumor Bank Tumor Tissue Work base behavior influence cancer cell cell type college cytokine extracellular granulocyte host neoplasm interaction human tissue imaging modality in vivo in vivo imaging innovation loss of function macrophage malignant breast neoplasm migration monocyte mouse model neoplastic cell neutrophil novel overexpression pre-clinical precursor cell prognostic prognostic value programs release factor response stem trafficking trait tumor tumor microenvironment tumor progression working group

项目摘要

DESCRIPTION (provided by applicant): This application seeks support for four linked research projects focused on the influences of components of the tumor microenvironment on the progression of primary tumors and metastases using both human tumor materials, cell biological methods and genetically engineered mouse models of cancer, with particular emphasis on breast and lung cancer. The microenvironment of tumors contains many non-tumor cells, including macrophages, neutrophils and myofibroblasts and several of the projects use both mouse models and human patient samples to investigate the influences of these cells on the behavior of the tumor cells - both locally derived as well as systemically recruited cells from the bone marrow and elsewhere (e.g., spleen).The generation and trafficking of these cells will be analyzed using sophisticated in vivo imaging methods in both mouse models and human patients. The secreted signals (growth factors and cytokines) that recruit and program these cells of the "reactive tumor stroma" will be investigated as will be the mechanisms of their effects on the tumor cells - induction of EMT, acquisition of stem-cell-like properties, migration, invasion, intravasation and extravasation and formation of metastases. The reactive stroma also contains a complex extracellular matrix (ECM), which includes bound growth factors and cytokines and the composition of this ECM changes markedly during tumor progression - these changes will be analyzed in detail using newly developed proteomics methods and their functional significance will be analyzed by manipulating the expression of relevant genes in both tumor and stromal cells. The four project leaders have a history of productive interactions and collaborations that will be further enhanced by TMEN support. The combined use of human patient material to anchor the discoveries to clinically correlated criteria and mouse models for investigation of the causality of the identified interactions in pre-clinical tests will allow progess possible with neither system alone. The common goal of these projects will be to dissect the cellular and non-cellular effects of the tumor stroma on tumor progression with a view to identifying novel biomarkers and signatures of diagnostic and prognostic value and new targets for potential therapeutic intervention.

描述（由申请人提供）：本申请寻求对四个关联的研究项目的支持，这些研究项目着重于使用人类肿瘤材料，细胞生物学方法和基因工程小鼠模型的肿瘤微环境对原发性肿瘤和转移酶进展的影响，并特别强调乳腺癌和肺癌。肿瘤的微环境包含许多非肿瘤细胞，包括巨噬细胞，中性粒细胞和肌成纤维细胞，几个项目都使用小鼠模型和人类患者样品来研究这些细胞对肿瘤细胞的影响对局部衍生的肿瘤细胞的影响 - 既可以衍生出来，既可以使用这些细胞，又是从骨骨髓和其他地方招募的细胞（E.G. E.G.，E.G.，E.G.，E.G. e.g.，分析），分析和分析。小鼠模型和人类患者的体内成像方法精致。将研究和编程“反应性肿瘤基质”细胞的分泌信号（生长因子和细胞因子），这将是它们对肿瘤细胞作用的机制 - 诱导EMT的诱导，类似干细胞的特性，迁移，迁移，迁移，，转移酶的入侵，侵入和渗出和形成。反应性基质还包含一个复杂的细胞外基质（ECM），其中包括结合生长因子和细胞因子，并且在肿瘤进展过程中，该ECM的组成显着变化 - 这些变化将使用新开发的蛋白质组学方法进行详细分析，并且它们的功能意义将通过操纵相关细胞的表达来分析，并分析其功能意义。这四个项目领导者有生产性互动和协作的历史，TMEN支持将进一步增强。人类患者材料将发现锚定在临床相关的标准和小鼠模型中，以研究临床前测试中已识别相互作用的因果关系，将允许单独使用系统。这些项目的共同目标是剖析肿瘤基质对肿瘤进展的细胞和非细胞作用，以识别新型的生物标志物和诊断和预后价值的特征以及潜在治疗干预的新目标。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Metastatic cells will take any help they can get.

DOI：
10.1016/j.ccr.2011.11.022
发表时间：
2011-12-13
期刊：
Cancer cell
影响因子：
50.3
作者：
Hynes RO
通讯作者：
Hynes RO

LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia.

DOI：
10.14309/ctg.0000000000000272
发表时间：
2020-12-22
期刊：
Clinical and translational gastroenterology
影响因子：
3.6
作者：
Neyaz A;Odze RD;Rickelt S;Nieman LT;Bledsoe JR;Mahadevan KK;Arora K;Jeck WR;Taylor MS;Gala M;Patil DT;Yilmaz OH;Rivera MN;Ting DT;Deshpande V
通讯作者：
Deshpande V

Tackling the cancer stem cells - what challenges do they pose?