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(7) Novel imaging devices for measurement and control of tumor microenvironments

(7)用于肿瘤微环境测量和控制的新型成像装置

基本信息

批准号：
9900579
负责人：
JOHN S CONDEELIS
金额：
$ 57.96万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9900579
关键词：
Address Affect Anatomy Animals Antibodies Area Biological Biological Process Biological Products Biological Sciences Biophysics Blocking Antibodies Breast Breast cancer metastasis Cancer Biology Cancer Model Catalogs Cell Density Cell physiology Cell surface Cells Cellular biology Cessation of life Chemical Agents Chemicals Correlative Study Diagnosis Disease model Dose Endothelial Cells Evolution Expression Profiling Extracellular Matrix Fluorescent Antibody Technique Gene Expression Profiling Hypoxia Image Imaging Device Immune In Vitro Individual Investigation Label Light Location Lung Malignant Neoplasms Mammary Neoplasms Measurement Microfluidics Microscopy Modeling Molecular Multimodal Imaging Mus Neoplasm Metastasis Optics Pathologist Phenotype Physics Primary Lesion Primary Neoplasm Process Reaction Time Recurrence Research Personnel Resolution Risk Role Secondary Lesion Signal Pathway Signal Transduction Site Stains Stromal Cells Structure Supporting Cell System Techniques Technology Testing Therapeutic Time Tissue Stains Tissue imaging Tissues Uncertainty Woman Work behavioral phenotyping cell behavior cell motility cell type chemotherapy density design driver mutation experience experimental study fluorescence lifetime imaging human tissue in vivo in vivo imaging interest intravital imaging laser capture microdissection macrophage malignant breast neoplasm materials science mimetics mouse model movie neoplastic cell novel novel imaging technology novel strategies physical science prevent prognostic value programs response sample fixation targeted agent tool tumor tumor heterogeneity tumor microenvironment tumor progression

项目摘要

PROJECT SUMMARY/ABSTRACT Understanding the identity, location and function of cells in the tumor microenvironment is essential to understanding how they dominate tumor phenotype and contribute to dissemination and metastasis. An example of this is the tri-partite structure TMEM (for Tumor MicroEnvironment of Metastasis) consisting of the juxtaposition of a macrophage, an endothelial cell and a tumor cell which function together to act as the doorway for metastatic dissemination. We have created novel imaging technologies consisting of 1)implantable windows with embedded microfluidics that allow serial high-resolution, single-cell microscopy of the primary and metastatic sites over days to weeks, and 2)multi-modal image alignment technologies to register fixed, stained, tissue sections to each other or to the acquired intravital imaging movies. Light activated valves embedded in the microfluidic system will be used to deliver microenvironment-altering chemical (e.g. hypoxia mimetics, chemotherapy) and biological (e.g. function blocking antibodies) agents and label unmarked tissues with fluorescent antibodies, all while imaging the tissue response in real time. Intravital imaging will be used to image the tissue and provide single-cell resolution images that cover the entire tissue over time spans ranging from seconds, to days, and even weeks. Finally, motile cells will be captured, either by chemo-attraction to microfluidic chambers, or laser capture microdissection after fixation, for further expression profiling. Application of these technologies to the study of primary and secondary lesions an unprecedented ability to probe the identity, location, quantity and function of the cells composing the heterogeneous microenvironment. Further, testing, in vivo, the targeting agents affecting the distribution, function and dynamics of the cells forming TMEM, as well as and the cells with which they interact, will enable the rapid determination of those agents with best therapeutic potential. This work will determine how 1) hypoxia, ECM density, immune cell density and chemotherapy initiate and define tumor heterogeneity in the primary and secondary sites; 2) chemotherapy and known blockers of TMEM assembly and function affect the dynamics of intravasation and dissemination in the primary and secondary sites; and 3) the relationship between cellular behavior and phenotype with cellular identity and location. The techniques utilized in this project are generally applicable and will allow molecular identification, localization and quantification of tumor heterogeneity in many cancers and disease models.

项目总结/文摘