Tumor Microenvironment and Metastasis

肿瘤微环境与转移

基本信息

批准号：
9122703
负责人：
Israel DAVID GOLDMAN
金额：
$ 33.13万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9122703
关键词：
Actins Address Adhesions Albert Einstein Cancer Center Attention Basement membrane Biochemical Biophotonics Biosensor Blood Blood Circulation Blood Vessel Tissue Blood Vessels Brain Cadherins Cancer Center Cancer Center Support Grant Cause of Death Cell Communication Cell Line Cell Proliferation Cell physiology Cells Chemotaxis Communities Correlative Study Cytoskeletal Proteins Cytoskeleton Data Development Dissection Distant Elements Endometrial Carcinoma Endothelial Cells Environment Epithelial ErbB Receptor Family Protein Estrogen Receptors Event Extracellular Matrix Extravasation Goals Grant Growth Factor IL8RB gene Image Imaging technology In Vitro Inflammatory Instruction Integrins Intercellular Junctions Invaded Knowledge Label Life Liver Lung Macrophage Colony-Stimulating Factor Receptor Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Malignant neoplasm of prostate Mechanics Membrane Metastatic to Modeling Molecular Molecular Profiling Mouse Cell Line Mus Mutation Neoplasm Metastasis Oligosaccharides Organ Paper Pathway interactions Patients Peer Review Peer Review Grants Pharmaceutical Preparations Phase Phenotype Play Primary Neoplasm Process Prognostic Marker Program Research Project Grants Property Proteins Proteolysis Publications Regulation Research Research Design Resource Sharing Risk Role Signal Pathway Signal Transduction Site Stream Stromal Cells Surface System Testing Therapeutic Intervention Time Tissues Transgenic Model Translating Tumor Cell Invasion United States National Institutes of Health Xenograft procedure angiogenesis base cancer cell cell behavior cell growth cell motility chemokine receptor cytokine genetic approach human tissue in vivo innovative technologies interest macrophage malignant breast neoplasm member migration monocyte mortality mouse model mutant neoplastic cell new technology novel optical imaging prevent programs receptor sensor therapeutic target tool tumor tumor microenvironment tumor progression

项目摘要

PROJECT SUMMARY (See instructions): The Tumor Microenvironment and Metastasis Program focuses on the interactions between cancer cells and their microenvironment that are determinants of the potential of tumor cells to invade surrounding tissues, penetrate blood vessels, and ultimately enter and grow in distant tissues. Studies are directed to deciphening the signaling pathways and mechanical interactions among monocytes, macrophages, endothelial cells and carcinoma cells, and each of their supporting stroma, which contribute to the metastatic phenotype. The goals of the program are to: (1) Dissect the role the microenvironment in tumor progression and metastasis, in particular, the contribution of macrophage subpopulations to the various phases and elements of tumor progression; 2) to elucidate the molecular mechanisms of growth factor and cytokine action in regulating cell migration, dissemination, angiogenesis and invasion of distant sites by primary tumor cells; 3) to assess the role of surface molecules, such a cadherins and membrane surface oligosaccharides, in tumor progression; (4) to characterize the biochemical and structural properties of molecules that regulate cytoskeletal proteins involved in tumor cell and macrophage motility through the development of (i) fluorescent biosensors of the activity status of pathways involved in regulating cell migration in vivo and (ii) photo-switchable proteins for quantitative long-term tracking of distinct groups of cells photomarked in the primary tumor and (5) to translate these findings into correlative studies with human tissues that are predictive of metastatic potential and risk, and that identify therapeutic targets. New imaging technologies are developed in the Gruss Lipper Biophotonics Center that provides this program with unique tools that are made available to the broader AECC community through the Analytical Imaging Shared Resource. Intrinsic to the experimental approach is the development of novel mouse transgenic models with fluorescently-labeled cellular lineages. The research by members of this program is integrated by a major shared focus on breast cancer, although other tumor types are studied as well. Research in this program is supported, in part, by a program project grant which reflects, and furthers, the collaborative research of members of this program. There are currently 24 members from 11 departments, of whom 10 are new to the program, supported by 22 NCI grants ($4.1M Direct) and 18 other peer-reviewed cancer-relevant grants ($3.5M Direct). Since the last CCSG review there have been 239 cancer-relevant research papers by members of this program of which 23% represent intraprogrammatic, and 28% represent interprogrammatic publications.

项目摘要（参见说明）：肿瘤微环境和转移计划重点关注癌细胞与其微环境之间的相互作用，这些相互作用是肿瘤细胞侵入周围组织、穿透血管并最终进入远处组织并在其中生长的潜力的决定因素。研究旨在破译单核细胞、巨噬细胞、内皮细胞和癌细胞及其每种支持基质之间的信号传导途径和机械相互作用，这些因素有助于转移表型。该项目的目标是：（1）剖析微环境在肿瘤进展和转移中的作用，特别是巨噬细胞亚群对肿瘤进展的各个阶段和要素的贡献； 2）阐明生长因子和细胞因子作用调节原发性肿瘤细胞迁移、扩散、血管生成和远处侵袭的分子机制； 3) 评估表面分子（例如钙粘蛋白和膜表面寡糖）在肿瘤进展中的作用；（4）通过开发（i）参与调节体内细胞迁移的通路活性状态的荧光生物传感器和（ii）照片来表征调节参与肿瘤细胞和巨噬细胞运动的细胞骨架蛋白的分子的生化和结构特性-可切换蛋白，用于定量长期跟踪原发肿瘤中光标记的不同细胞群，以及（5）将这些发现转化为与人体组织的相关研究，预测转移潜力和风险，并确定治疗靶点。格鲁斯利珀生物光子学中心开发了新的成像技术，为该计划提供了独特的工具，这些工具可通过分析成像共享资源提供给更广泛的 AECC 社区。该实验方法的本质是开发具有荧光标记细胞谱系的新型小鼠转基因模型。该计划成员的研究主要集中在乳腺癌上，尽管也研究了其他肿瘤类型。该计划的研究部分由计划项目拨款支持，该拨款反映并进一步促进了该计划成员的合作研究。目前有来自 11 个部门的 24 名成员，其中 10 名是该计划的新成员，由 22 项 NCI 拨款（410 万美元直接拨款）和 18 项其他经过同行评审的癌症相关拨款（350 万美元直接拨款）支持。自上次 CCSG 审查以来，该计划成员已发表 239 篇与癌症相关的研究论文，其中 23% 代表计划内出版物，28% 代表计划间出版物。