Tumor-Stroma Interacions in the Tumor Microenvironment

针对肿瘤微环境网络（TMEN）RFA的这一应用将重点关注 癌症开始和进展的小鼠模型，特别是在乳腺和肺中，并且涉及两者 可移植的和自体的（即自发的内源性）肿瘤。申请团体为 多学科，涉及小鼠模型，癌细胞生物学，分子成像和 蛋白质组学单个子项目将侧重于肿瘤微环境的特定组成部分; 细胞、分泌因子和细胞外基质（统称为基质），以及基质的性质。 对癌症的免疫反应。 我们将研究以下主题： 1.基质对肿瘤细胞最初为什么和如何成为侵袭性和转移性的影响， 在原发性肿瘤部位的间质效应的结果。 2.可以抑制或增强转移瘤的播种、存活和生长的微环境效应 在第二个站点。 3.基质细胞（间充质和造血）的身份和起源诱导，或招募到， 原发性肿瘤的部位，它们如何被招募，以及它们如何影响肿瘤的进展 4.自体肿瘤免疫监视的本质 5.不同肿瘤细胞外基质（ECM）的性质以及肿瘤和基质的相互作用 细胞外基质 6.我们将进一步开发新的成像探针和方法，以检测，跟踪和消融不同的亚群， 小鼠癌症模型中的基质细胞。 7.我们将使用慢病毒介导的RNA干扰来启动自体肿瘤， 肿瘤细胞和基质细胞的功能。 越来越多的人认识到，肿瘤细胞不会孤立地发展为恶性肿瘤， 肿瘤的微环境可以增强或抑制肿瘤生长和进展。这个程序 将提供新的信息和新的技术方法的问题，有关的影响， 肿瘤生长的微环境。预计这项研究的新见解 将为干预肿瘤向恶性发展提供新的方法。

This application in response to the RFA for the Tumor Microenvironment Network (TMEN) will focus on mouse models of cancer initiation and progression, particularly in the breast and lung and involving both transplantable and autochthonous (i.e. spontaneous endogenous) tumors. The applicant group is multidisciplinary, involving investigators expert in mouse models, cancer cell biology, molecular imaging and proteomics. The individual subprojects will focus on specific components of the tumor microenvironment; cells, secreted factors and extracellular matrix (collectively termed stroma), as well as on the nature of the immune response to cancer. We will investigate the following topics:- 1. stromal influences on why and how tumor cells initially become invasive and metastatic as a consequence of stromal effects at the site of the primary tumor. 2. microenvironmental effects that can suppress or enhance the seeding, survival and growth of metastases at secondary sites. 3. the identity and origins of stromal cells (mesenchymal and hematopoietic) induced at, or recruited to, the site of a primary tumor, how they are recruited, and how they affect the progression of the tumor 4. the nature of immune surveillance of autochthonous tumors 5. the nature of different tumor extracellular matrices (ECMs) and interactions of both tumor and stromal cells with ECM 6. we will further develop novel imaging probes and methods to detect, track and ablate different subsets of stromal cells in mouse models of cancer. 7. we will use lentiviral-mediated RNA interference both to initiate autochthonous tumors and to manipulate the functions of both tumor and stromal cells. It is becoming increasingly recognized that tumor cells do not progress to malignancy in isolation - the microenvirnment of the tumor can either enhance or suppress tumor growth and progression. This program will provide new information and novel technological approaches to questions concerning the effects of the surrounding microenvironment in which tumors develop. It is expected that new insights from this research will offer novel approaches to intervene in the progression of tumors to malignancy.