Tumor-Stroma Interacions in the Tumor Microenvironment

本应用程序针对肿瘤微环境网络(TMEN)的RFA将重点关注 肿瘤发生和发展的小鼠模型，特别是在乳腺癌和肺癌，并涉及两者 可移植和自体(即自发的内源性)肿瘤。申请者组为 多学科，涉及老鼠模型、癌细胞生物学、分子成像和 蛋白质组学。各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 对癌症的免疫反应。 我们将调查以下主题： 1.间质对肿瘤细胞最初成为侵袭和转移的原因和方式的影响 原发肿瘤部位间质效应的后果。 2.抑制或促进转移瘤播种、存活和生长的微环境效应 在辅助站点。 3.骨髓基质细胞(间充质细胞和造血细胞)的特性和来源。 原发肿瘤的位置，它们是如何被招募的，以及它们如何影响肿瘤的进展 4.原发肿瘤的免疫监视性质 5.不同肿瘤细胞外基质的性质及肿瘤与间质的相互作用 带有ECM的细胞 6.我们将进一步开发新的成像探针和方法，以探测、跟踪和消融不同的子集。 小鼠癌症模型中的间质细胞。 7.我们将使用慢病毒介导的rna干扰来启动和操纵原位肿瘤。 肿瘤细胞和间质细胞的功能。 越来越多的人认识到，肿瘤细胞不会在孤立的情况下进展为恶性肿瘤-- 肿瘤的微环境可以促进或抑制肿瘤的生长和发展。本节目 将提供新的信息和新的技术方法来解决有关 肿瘤生长的周围微环境。预计这项研究的新见解 将提供新的方法来干预肿瘤向恶性肿瘤的进展。

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.